SELECTED STUDIES


Preventive Genetics (Part I)

 

Genetic Toxicology Research in Developing Countries:

 

By Prof. Wagida A. Anwar, M.D.

 

 

Introduction

 

Developing countries are currently facing the new challenges of advancement in molecular genetics whether at the educational or research level. This progress could improve diagnosis, treatment, understanding of disease risk factors, and prevention.

 

A major area of concern is environmental health, which comprises those aspects of human health, disease, and injury that are determined or influenced by factors in the environment. This includes the direct pathological effects of various chemical, physical, and biological agents, as well as the effects on the broad social environment, which includes housing, urban development, land-use, transportation, industry, and agriculture (WHO, 1997). Currently, there is a growing interest to the use of different biomarkers and genetic susceptibility testing, which can contribute effectively in risk assessment. Biomarkers can be used to detect the effects of environmental pollutants before adverse clinical health occurs.

 

Developing countries have unique environmental exposures and public health circumstances, which makes it ideal for environmental mutagenicity and carcinogenicity research. There are exposures to chemical genotoxicants (e.g., automobile exhaust, pesticides, metals and cytotoxic drugs) and to lifestyle factors (e.g. consumption of tobacco products) that have been linked to the expression of biological effects and to increased risk for cancer. Infections can be associated with cancer development when the environmental factors interact with the infection and lead to the enhancement of the carcinogenic process. The high prevalence of viral pathogens and the improper use of pesticides may endanger biological functions beyond those for which they originally manufactured.

 

Genetic Toxicology of Chemicals


Mutagenicity and carcinogenicity are highly regarded as toxic effects because they can occur in the absence of other toxic effects and long after exposure. Although these concerns are valid, they should not preclude the assessment of other more proximal toxicities. Thus, the possible teratogenicity, immunotoxicity, or embryotoxicity of a chemical should be considered with mutagenicity/carcinogenicity data when assessing overall hazard.

 

It is of utmost importance to assess the possible impact of environmental mutagens/carcinogens on human health. Named pollutants (e.g., pesticides) are easy to recognize, but they may not be the most important agents present. Several scientists decide that endogenous mutagens must be tolerated and that emphasis should be placed on the detection and assessment of man-made pollutants. This is acceptable so long as the implicit compromise of acceptable risk is recognized. Sometimes this compromise may be unacceptable, as in an environment known to be rich in natural nitrosamines; however, such knowledge can only come from an evaluation of chemical pollutants.

 

Inspecting the chemical structure of an agent for sites of actual or potential electrophilicity provides a useful primary screen for agents with an enhanced chance of being mutagenic and/or carcinogenic to several species, including humans. Such an analysis can be based on chemical knowledge or can be assisted by computerized structure-activity systems. Such structural alerts, however, only provide an indication for the need to evaluate the toxicity of an agent. They do not remove the need to conduct such tests.

 

Several International Agencies such as the International Programme on Chemical Safety, WHO, The U.S. Environmental Protection Agency and the European Chemical Industry Ecology and Toxicology Center provided sources of toxicity/mutagenicity data on major commodity chemicals. On the other hand, suppliers may be the only source of data on new chemicals. Only when sources of data have been exhausted should new studies be commissioned on a chemical. In cases where additional mutagenicity data are required before a hazard assessment can be made, it is preferable to build these studies on the internationally agreed base of assays.

 

Carcinogenicity data can be obtained from the International Agency for Research on Cancer database, WHO, the U.S. National Toxicology Program carcinogen database, or from the suppliers of chemical in the case of major products. Finally, updated information can also be obtained from the current scientific literature. From such an analysis, it is usually possible to assess the mutagenic/carcinogenic hazard of an agent without additional testing. Such precautionary searches will enable the limited resources available in developing countries to be used on agents of importance to the environment and for which no data exist. Unfortunately, it is common to find scarce resources in a developing country for evaluating a chemical, even when the agent is of known genotoxicity in developed countries and the chemical may even be banned or controlled in those countries.

 

The question of chemical mixtures is an ever-present problem in all countries. Not only may synergistic or antagonistic effects be produced in mixture, but also genotoxic effects considered negligible on an individual chemical basis may become significant when integrated into a mixture. Documentation of mutagenic effects in exposed populations and assessment of the mutagenicity of representative mixtures derived from an environment can provide input of hazard ranking, although international responses to data on mixtures remain unclear.

 

Prioritization of chemical hazards commences with published information. Additional mutagenicity experiments and human surveillance studies flow from such analysis, but should not replace them. These considerations are of great importance in countries with limited resources and with perhaps more important human health problems that must be addressed.

 

Human Surveillance Studies

 

A wide variety of techniques for monitoring genetic damage induced in humans by environmental chemicals or environment factors are now available. Rapid advances in improving the sensitivity of such the techniques are being made, emphasis was placed on the proper use of these techniques, and the following points emerged:

·        Populations selected for study should be influenced by a clear perception of the relative hazards in the given country or environment.

·        Specific attention should be given to the experimental design of studies, in particular, the selection of appropriate and concurrent control groups, the choice of adequate group sizes, the elimination of confounding variable, the use of coded samples for analysis, and the selection of vigorous statistical methods for the evaluation of data.

·        Attempts should be made, wherever possible, to include an intervention aspect to the study (e.g., the study of individuals before they enter the polluted environment, the follow-up of those who leave it, and monitoring the effect of selective removal of a suspect genotoxin from the environment under study).

·        The use of cytogenetic analysis in all studies on human blood is strongly recommended. This will enable a common point of comparison between studies using other end points (e.g., hemoglobin adducts, hprt mutations, sister chromatid exchange) and between studies performed in different countries and in time.

·        The current progress in human surveillance techniques suggests that refined methodologies will soon be available, and it will be important to reassess earlier studies using these new techniques. It is suggested that blood samples should be stored from all studies for further analysis. The possible role of the World Health Organization (WHO) in this task should be explored.

·        The possible role of lifestyle variables such as deficient diet, food contaminants and infection in modulating genetic outcome from exposure to mutagens is of particular importance in developing countries.

 

In summary, when a major genetic hazard is recognized, an important consequence is usually that the exposed humans will be monitored to quantify that hazard. In such cases, great care should be taken to optimize the derived data by adequately designing the studies. Human surveillance studies are the last point of intervention before the recognition of human disease via epidemiological/clinical observations-as such they deserve appropriate design and follow-up. At present, human surveillance studies tend to be conducted on limited budgets and at the discretion of individual investigators.

 

Long-Term Follow-up of Human Studies

 

Implicit in the use of human surveillance (genetic monitoring) techniques is that acutely induced genetic changes provide an indication of possible long-term carcinogenic or mutagenic effects. Although this provides a practical and conservative justification for such studies, there are few data to support the underlying assumption.

 

Therefore, attempts should be made to initiate appropriate long-term follow-up studies – specifically, that epidemiological methods be used to correlate the outcome of surveillance studies with eventual onset of disease.

 

Alternatively, in some cases where a population is identified as being exposed to a possible mutagen/carcinogen, blood samples could be stored for possible future use in the case of a subsequent epidemiological study revealing and increased cancer incidence in that population. In the absence of such follow-up studies, the present human surveillance methods will have to remain simply as means to indicate potential long-term health effects. The necessary follow-up studies will require the backing and administrative assistance of a central body such as WHO or IPCS.

 

An extension of the above discussion is the fact that ethical issues should be raised by the conduct of human surveillance studies without adequate follow-up studies. Thus, if the implied stimulus for mounting such a human surveillance study is the need to recognize and control human exposure to a potential human carcinogen/mutagen, actions should flow from the observation of a positive effect. At present, such actions often do not follow, simply because the significance to the individual of the positive surveillance data is not clear. Carefully constructed follow-up studies would break this circle of uncertainty.

 

Molecular Epidemiology Research in Egypt

 

Egypt shares most of the environmental problems of developing countries which resulted in the appearance and prevalence of communicable and non-communicable diseases. The unique circumstances of public health problems increased the attention to environmental mutagenicity and carcinogenicity research. Some examples are exposure to chemical genotoxicants (e.g., automobile exhaust, pesticides, metals and cytotoxic drugs) and to lifestyle factors (e.g. consumption of tobacco products) that have been linked to the expression of biological effects and to increased risk for cancer (Anwar  and  Gabal, 1991; Anwar, 1991;  Anwar, 1993;  Anwar, 1994; Anwar, and Wild, 1994; Anwar, et al, 1994a; Anwar, et al, 1994b; Anwar, and Shamy, 1995).

 

Biological carcinogenic agents are varied in the form of parasitic, viral, bacterial, and fungal agents. Infection can be associated with cancer development. Environmental factors may interact with infection and lead to enhancement of the carcinogenic process. The most common preventable biological carcinogenic agent in Egypt is schistosomiasis, followed by viral hepatitis and other oncogenic viruses. The high prevalence of viral pathogens (e.g. high endemic rates of hepatitis C viral infection), knowledge gained from studying gene-environment interactions would be very helpful for understanding and controlling disease risks around the world (Abdel-Aziz et al, 2000; Frank, et al, 2000; Nafeh, et al, 2000; Habib, et al, 2001).

 

In recent years, the incidence of cancer in Egypt has increased. A substantial number of Egyptians are suffering from primary hepatocellular carcinoma (PHC) which is mainly preceded by hepatitis B infection (National Cancer Institute, 2003). It has been shown that aflatoxins are potent carcinogens in a number of animal species. Aflatoxin B1 has been classified by the International Agency of Research on Cancer as a group I carcinogen. It has been suspected as causal agent in the induction of hepatocellular carcinoma (IARC, 1994). The role of aflatoxins in carcinogenesis is complicated by Hepatitis B virus infection (Anwar, 1993; Anwar, and Wild, 1994; Wild, et al, 1992).

 

Schistosoma heamatobium infection is one of the most common health problems in Egypt. It is strongly associated with the development of urinary bladder carcinoma (Rosin, and Anwar, 1992; Rosin, et al, 1994a; Rosin, et al, 1994b; Hirvonen, et al, 1996).

 

Lung cancer, which is mostly related to air pollution and smoking, is more common in urban cities than rural villages. In urban areas, exposure to low levels and short-term peak levels of engine exhausts are ubiquitous. Higher exposures to engine exhausts may occur in some occupations such as that of traffic policemen. Consequently, they have been shown to increase chromosome damage and the damage was enhanced further by smoking (Anwar, and Kamal, 1988).

 

The improper use of pesticides may endanger biological functions beyond those for which they originally manufactured. Adverse effects may be caused not only by the active ingredients and the associated impurities, but also by the solvents, carriers, emulsifiers and other constituents of the formulated products (Al –Saleh, 1994). Potential exposure from the environment can be estimated by environmental monitoring. Actual exposure (uptake) is measured by biological monitoring of human tissues and body fluids.  Biomarkers are used to detect the effects of pesticides before adverse clinical health occur (Anwar, 1997). Agricultural workers exposed to pesticides showed increased incidence of chromosomal aberrations and sister chromatid exchanges (Anwar, 1994).

 

Around the world, an emphasis is on understanding genetic susceptibility to the development of environmentally related cancers. An initial focus was on the inheritance of variant chemical metabolizing genes on the development of cancers (Anwar, et al, 1996; NIEHS, 1997; Au, et al, 1999a; Au, et al, 1999b.  Another focus is on children’s susceptibility to environmental health problems. Egypt needs to develop international collaborative projects in these two priority areas to address our environmental health concern.

 

Need for Training Programs

 

There is a critical demand of qualified scientists in these fields, it is important to develop Training Programs. These programs can be implemented in collaboration with different collaborating centers, which will form a good partnership to provide short-term and long-term training opportunities. The training programs include laboratory work in molecular biology/genomics, cell biology, and proteins and bioinformatics. They are designed for the continuing education of research physicians and technicians in academic and industrial laboratories who want to enhance their knowledge and skills in the latest biotechnology areas.

 

These programs could actively coordinate, strengthen, and encourage collaboration between the various disciplines. They give a chance for a wider understanding of biotechnology through the introduction of a seminar series, and postgraduate training opportunities.

 

Developing country researchers who conduct health research in their countries need to learn about their experiences with current ethics rules and regulations. Training programs will bolster resources to provide the important bioethical perspective as well as increasing the awareness of investigators and institutions of the social, ethical, and legal aspects of modern genetics research, medical practice and in business management programs.

 

Need for International Coordination

 

The collaboration between universities and different research institutions, at the national and international level, is a necessity and consistent with fulfilling the priority for intersectoral cooperation for achieving significant improvement in environmental health and disease prevention.

 

All countries have regulatory authorities whose responsibility is to monitor the safety of key imported or domestic chemical such as pesticides and herbicides. Often these authorities consider only potential new registrations. It is therefore easy for the situation to develop wherein extreme attention is paid to a few new chemicals are essentially ignored, unless arbitrarily selected for study by individual investigators. A pressing need, therefore, is for a central agency in each country to be responsible for assessing the relative hazards in the environment and for prioritizing chemicals for study. Ideally, individual mutagenicity studies and human surveillance studies should be conducted considering these countrywide priorities. Further, there is an evident role for international coordination of information on the major chemicals of commerce, including agrochemicals, pesticides, and herbicides. Decisions to use a particular chemical will vary depending on local needs, but the toxicological profile of such chemicals should be internationally available as a primary input to such decisions.

The scientific community plays a crucial role in understanding the environmental causes of human health problems, and in collaborating with communities, industries and government agencies in resolving health problems. 

 

International Conferences on Environmental Mutagens

 in Human Populations – Opportunities, Accomplishments and Challenges

 

The field of environmental mutagenesis has been gaining international recognition for many years. The well-recognized pioneers who had promoted this field, particularly at the international level, are the late Dr. Alexander Hollaender and the late Dr. Frederick Sobel.  Through their independent efforts, they have organized workshops and conferences in countries where the field of environmental mutagenesis was non-existence. From these activities, many scientists in these countries have received education and training to initiate their careers and scientific societies that are committed to the field of environmental mutagenesis. With dedicated effort from many scientists, the initiatives from the late Hollaender and the late Sobel continued to flourish and became sustainable programs. Many of these programs are promoted by the EMS-Hollaender Fund for International Programs and the International Association for Environmental Mutagen Societies.  One sustainable program is the series of conferences known as the International Conference on Environmental Mutagens in Human Populations.

 

During 1987 and 1988, Dr. Wagida Anwar from Egypt was the visiting scientist in the University of Texas Medical Branch, Galveston, Texas, USA to conduct research studies in collaboration with Dr. William Au. They also considered opportunities in organizing outreach activities such as conferences.  They recognized that the series of international conferences on environmental mutagens have been organized every four years but these conferences are held specifically in well-developed countries.  There was a lack of such conferences of the similar caliber that are held in developing countries.  They also recognized that many scientists from the latter countries would not have the opportunity to travel to other countries to attend international conferences. Therefore, they decided to organize a series of conferences that would be held in countries where the field of environmental mutagenesis is in the developmental stages and where environmental health is of major concern locally and regionally.  The overall objectives are to enhance the awareness of and to identify solutions to human environmental health problems, to facilitate interactions and to foster international collaborations.

Dr. Au and Dr. Anwar planned to have the first conference in Cairo, Egypt, the hometown of Dr. Anwar. They brought their idea to Dr. Sobel (at that time, Dr. Hollaender had passed away already) with the anticipation that they would have to answer a lot of difficult questions, such as their experience in organizing international conferences and the financial commitment to the conference. Dr. Sobel maintained his positive attitude towards the proposal and took an active role in soliciting international sponsorship. With his help, the conference received support from many sponsors, notably the EMS-Hollaender Fund for International Programs and the International Association for Environmental Mutagen Societies. In collaborating with several scientific societies and government agencies the First International Conference on Environmental Mutagen in Human Populations was held in Cairo, Egypt, January 19-24, 1992 (Au, et al, 1993 and Ashby et al, 1993). The meeting sparked the interest in addressing environmental health concerns among scientists in the African Continent and stimulated the organization of the Pan African Environmental Mutagen Society.  Also, the Cairo conference was so successful that the participants requested the organization of additional conferences according to the similar topic. Subsequent meetings were organized in Czech Republic (1995), Thailand (1998), Brazil (2003) and will be in Turkey in 2007. All previous conferences were tremendously successful and they generated numerous new collaborations and sustainable programs.

 

THE CAIRO CONFERENCE, 1992


The first international conference on environmental mutagens in human populations (1st ICEMHP) was held in Cairo, Egypt, January 19-24, 1992. Wagida Anwar and William Au were co-chairpersons for the conference. 

The objective of the conference was focused on the state of knowledge on environmental, biological, genetic and reproductive problems affecting humans from exposure to environmental mutagens. The six-day conference was organized into symposia, oral contributed presentations, poster sessions and workshops.  The conference attracted over 200 participants and 199 abstracts from 31 countries. More than half of the participants were from the Middle East and Africa.  Invited speakers were requested to submit manuscripts of their presentation for publication in the meeting monograph. The monograph was published in Environmental Health Perspectives (Au et al., 1993). With 56 manuscripts in 338 printed pages, the monograph is an impressive issue. These accomplishments certainly justify international status of the conference and the value of hosting the meeting in countries where the field of environmental mutagenesis is in the developmental stages.

 

 

 

The enormous interest generated from the conference led to the development of many high profile and sustainable programs. The most visible of them is that the conference sparked the activities of the Pan African Environmental Mutagen Society (PAEMS). Since then, the society has organized a scientific conference throughout Africa approximately every two years: Cairo, Egypt, 1993; Cape Town, South Africa, 1996; Harare, Zimbabwe, 1999; Cairo, Egypt, 2003 and Fes, Morrocoo, 2005. Many international collaborative projects were initiated based on interactions in the 1st ICEMHP. For example, Dr. Au and Dr. Anwar developed one of the first molecular epidemiology projects in Egypt (Anwar et al., 1996). Dr. Anwar became the first recipient of the EMS-Hollaender International Fellow award, 2000, She was elected Secretary General of the International Association of Environmental Mutagen Societies (IAEMS), 2005 and recently 2006, a Fellow of Collegium Ramazini, Italy.

 

The success of the 1st ICEMHP and the PAEMS conferences has attracted the attention and long-term support from several external sources, particularly from the National Institute of Environmental Health Sciences, USA.

 

tHE Prague conference, Czech Republic, 1995

      

The second International Conference on Environmental Mutagens in Human Populations (2nd ICEMHP) was held in Prague, Czech Republic, August 22 - 25, 1995. Dr. Sram and Dr. Au were the co-chairmen of the conference.

 A total of 220 scientists from 30 countries attended this conference. The high scientific level of all presentations and the enthusiasm among the participants provided strong endorsement for continued organization of the conferences in the 4-year period. Another positive characteristic was that the monograph from the conference was published in Environmental Health Perspectives within 9 months (Au and Sram, 1996).

As shown in the manuscripts from the conference (Au and Sram, 1996), novel and relevant information were presented.  For example, developing strong international cooperation by the genetic toxicology community was strongly recommended. The emphasis for these collaborative studies should be: the use of biomarkers in molecular epidemiology that can be interpreted with confidence in term of health risk, the application of data for diseases prevention, the importance of conducting prospective studies and the banking of tissue samples for future investigations. The updated genetic activity profile software from EPA was presented. The data can be used for the characterization of exposures to environmental mutagens in highly polluted areas. The new concern regarding endocrine disruptive chemicals in the environment, e.g. pesticides on reproductive functions, was presented. The enormous database regarding mutation of the p53 tumor suppressor gene and increased risk for cancer was reviewed.

Several presentations were made regarding the measurement of health effects among populations exposed to fallouts from the Chernobyl accident.  Results from the large scale studies on the effect of polymorphic metabolizing genes (GSTM1, GSTT1, NAT2 and CYP1A1) on the expression of different biomarkers was presented.  A presentation was made on the use of the challenge assay on chromosomes to detect DNA repair deficiency in exposed populations. A colorful presentation on the use of the fluorescence in situ hybridization (FISH) assay to detect aneuploidy in human sperm was well received.

For the first time, results from the Teplice Program, an extensive environmental and population studies in Northern Bohemia, Czech Republic, was presented in an international conference. The data indicate that the measurements of PAH exposure and DNA adducts were the best indicators for exposure to industrial discharge to the environment.  In addition, results on DNA adducts in placenta were related to the intensity of pollution in the studied areas.

The conference definitely high lighted the serious and potentially overlooked environmental pollution and health problems in the former Soviet countries. More importantly, the conference gathered a critical mass of scientists and provided the opportunity to develop collaborations to address the problems. The conference enhanced the value of the ongoing Teplice program.  In addition, the collaboration developed during the meeting was timely for these scientists to respond to the new research funding mechanism from the European Union.  The emphasis was to award grants to collaborations between member and non-member States.

 

THE Bangkok/Khao Yai CONFERENCE, Thailand, 1989

 

It is extraordinary to conduct an international meeting in two cities. To organizers of a meeting, it would have been a dreadful responsibility. However, the Thai organizers achieved the goal without any complications.  The meeting convened in Bangkok for two days. Then, the participants (over 200) and their luggage were bused to Khao Yai, a remote city in the mountain, which was about six hour of driving time away from Bangkok. At the end of the meeting, the participants needed to be bused back to Bangkok for their departure.  Khao Yai was obviously a major contrast to Bangkok in terms of size, social activities and geographical setting. Its small size and remoteness actually created tremendous opportunity for the participants to interact with each other for three days. By organizing the meeting in Thailand, scientists from many countries in the surrounding region were able to attend an international conference.  Notably are scientists from countries like Laos, Sri Lanka and Vietnam that had no scientific programs in the field of environmental mutagenesis.

The theme for the Third International Conference on Environmental Mutagens in Human Populations (3rd ICEMHP) in Thailand was “Understanding Gene and Environmental Interactions for Disease Prevention”. The theme was addressed in the following 9 important topics: Mechanisms of Mutagenesis and Carcinogenesis, Methods to Detect Exposure and Effects of Genotoxic Agents, Metabolic Influences on Cancer Susceptibility, Genetic Susceptibility Influencing Disease Outcome, Prospects for Cancer Prevention, Influences of Environmental Mutagens in Different Countries, Germinal and Reproductive Effects of Environmental Mutagens, forum on Issues in Safety and Health Assessment and Forum on Developing Sustainable Studies on Environmental Health.  Manuscripts from presentations in the conference were published in Mutation Research (Au et al., 1999). The conference monograph was published within 10 months from the conference.

Several unique events took place in the 3rd ICEMHP conference. One was the presentation of an International Mutation Research Award for Excellence in Scientific Achievement to Dr. Minako Nagao, National Cancer Institute, Japan.  Another was the presentation of Continuing Educational Credits from the American Medical Association through the University of Texas Health Center at Tyler by Dr. Arthur Frank.  Five participants with outstanding presentations were awarded each with a five-year free subscription to the scientific journal, Environmental and Molecular Mutagenesis.

From the successful organization of the 3rd ICEMPH, the Thailand Environmental Mutagen Society (TEMS) became better organized and better recognized locally and internationally.  TEMS was invited to be a counterpart of the Toxicology Association of Thailand and was awarded the opportunity to organize the 3rd International Conference of Asian Society of Toxicology (3rd ASIATOX) in 2003. Cooperation and collaboration among the members were increased significantly.  Members from Chulalongkorn University, Mahidol University (2 faculties), National Cancer Institute and National Institute of Dermatology received funding from the National Center of Genetic Engineering and Biotechnology for a large project to investigate the health impact of natural mutagens and carcinogens. A member, Suparp Keithubthew, received a EMS-Hollaender International Trainee fellowship. With the training, she developed a molecular epidemiology program in Thailand (Kietthubthew et al., 2001).

TEMS became more successful in raising funds in support of a variety of functions. For example, funds were provided to 8 Thai scientists from 4 universities and 1 Burmese health personnel to obtain technical training, to the Ministry of Interior to help flood victims in northern and southern Thailand in 2000 and 2001, to a Mahidol student who was ill with cancer to defray the hospital expenses and to a junior scientist for travel expenses to present a paper in The 8th International Conference in Environmental Mutagens in Shizuoka, Japan in October, 2001.

With the organization of three highly successful international conferences, the series become a well-respected international activity. Therefore, the International Association for Environmental Mutagen Societies has officially adopted the series into its portfolio of activities.  The series can now enjoy the recognition and support from the EMS-Hollaender Fund for International Programs, the National Institute of Environmental Health Sciences, the Environmental Protection Agency and the International Association of Environmental Mutagen Societies.

 

Florianopolis-SC CONFERENCE, Brazil, 2003

 

 

 

 

The 4th International Conference on Environmental Mutagens in Human Populations (4th ICEMHP) will be held in Brazil.  The conference will follow the similar structure and pattern already seen in the previous conferences in the sense that it will also be designed to identify solutions to human environmental health problems and to facilitate the establishment of sustainable collaborative programs in the region and around the world. This Conference will focus on environmental exposure, genetic effect, health impact of environmental pollutant and individual susceptibility. In this post-genoma era, the Conference will also focus on themes such as the identification of genes involved with environmental diseases,  use of genomics in understanding toxicological responses and the functional evaluation of polymorphic genes for susceptibility.  Specific symposium topics that are being organized are: 1) Mechanisms of mutagenesis and carcinogenesis, 2) Biomarkers for mutagen exposure and for prediction of health risk, 3) Health impact of environmental pollutants, 4) Genetic and acquired susceptibility to environmental disease, 5) Genome-based technology for toxicology and health, 6) Health impact of food-borne mutagens and antimutagens and 7) Unique concerns for environmental health in Latin America.

The people from Latin America will certainly take advantage of this opportunity to discuss their own concerns for environmental health, such as human health concerns with genetically modified crops, health concerns with the extensive use of pesticides and distribution of environmental cancer in Latin American countries.

The 4th ICEMHP will be held at the Costão do Santinho Resort, on the coast of Florianopolis-SC, Brazil, an ecological paradise with a large area covered with the Atlantic Forest and preserved dunes, where the sea, trees, and mountains will be awaiting for everybody.  Like the previous meetings, the quality of science will be outstanding.  Participants in this conference will anticipate gaining scientifically and socially rewarding experience.

 

The Fifth International Conference on Environmental Mutagens in Human Populations (Vth ICEMHP)

International Conferences on Environmental Mutagens in Human Populations: simple and persistent outreach effort with significant effect

 

Dr. Semra Sardas, Dr. Ali Karakaya and Dr. William Au co-chair the conference. The theme of the conference is “Identification of Environmental Hazards and Promotion of Health”.  The conference will be held in the beautiful and historical Mediterranean city, Antalya, Turkey, May 20 - 23, 2007.  The web-site for the conference is www.environmutagen2007.org.

 

Different Symposia will discuss the following topics:
 

1)      Mechanisms of mutagenesis and carcinogenesis

2)      Children Environmental Health

3)      Human monitoring for health risk evaluation and disease prevention

4)      Gene-Environmental interactions on health (To be organized and sponsored by the National Institute of Environmental Health Sciences)

5)      New technologies and frontiers in environmental health 

6)      Unique environmental health concerns and environmental disasters

7)      Transplacental and transgenerational exposures and health consequences

8)      Translation of scientific knowledge into public health practices

9)      Building environmental health infrastructure through science, education and outreach effort

Different Workshops will be organized  which will include:

1)      HUMN Project International Working Group on the micronuclei assay in human populations

2)      Community outreach and health promotion (National Center for Environmental Health and Agency for Toxic Substances and Disease Registry)

3)      Use of biomarkers in toxicology and population monitoring

 

In addition, short contributed oral presentations and Poster sessions will be organized

The invited keynote speakers are:

1)      Professor Dr. Her Royal Highness Princess Chulabhorn: Opportunities and challenges on environmental health in Southeast Asia. President, Chulabhorn Research Institute, Bangkok, Thailand.

2)      Dr. David Schwartz:  Scientific strategies to address environmental health problems.  Director, National Institute of Environmental Health Sciences, RTP, North Carolina

3)      Dr. Henry Falk: Improvement of public health, a national and international priority.  Director,  Coordinating Center for Environmental Health and Injury Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia

4)      Dr. James Gentile: Education and training for future research biologists.  President, Research Corporation, Tucson, Arizona

 

The Pan African Environmental Mutagen Society (PAEMS)

 

Realizing the importance of research on the relation between environmental pollutant exposures and their genetic effect, The Pan African Environmental Mutagen Society (PAEMS) has been established in 1983 to encourage research on environmental mutagenesis.  Its headquarters was located in Nairobi, Kenya. The first meeting was in Cairo 1993. The second was in Cape Town, South Africa 1996, the third conference was in Harare, Zimbabwe  in 1999, the Fourth was in Cairo, Egypt in 2003, the Fifth was in Fes, Morocco and the sixth will be in Cape Town, South Africa in 2008..

 

The main goals of the PAEMS are to spread the new information and technology concerning Environmental Mutagenesis and to clarify the possibility of cooperation and training programs between different African countries and other countries.

 

The main objectives of the PAEMS are:

1.To help African scientists to recognize and control their own problems.

2.To encourage the study of mutagens, carcinogens and substances of related biological activity in the human environment, particularly those of public health importance in Africa.

3.To facilitate the spread of information and technology concerning environmental mutagens and carcinogens.

4.To promote cooperation and training programmes between different African countries with leading laboratories and international agencies around the world. The PAEMS plans to organize regular scientific meetings in different African countries to discuss health problems of special importance to the African countries. This will help to disseminate the information to African countries.

During the "First International Conference on Environmental Mutagenesis in Human Populations at Risk, which was organized in Cairo during the period 19‑24 January 1992, A meeting of the Pan African Environmental Mutagen Society (PAEMS) took place to reactivate the society,  revise the constitution,  election of new office bearer and putting a plan for future activities. The meeting recommended the transfer of the headquarter of the society from Nairobi, Kenya to Cairo, Egypt at the Department of Community, Environmental and Occupational Medicine, Faculty of Medicine, Ain Shams University. Prof. Aly Massoud was nominated the President of the Society. Prof. Wagida Anwar was nominated Secretary General of the Society.  

The first activity of PAEMS was a two-day meeting on "mycotoxins as mutagens and carcinogens: possibilities for Disease Prevention" From 23-25 January, 1993. The meeting discussed the possible exposure conditions, monitoring methods, hazards of mycotoxins as mutagens and carcinogens, interactions between mycotoxins and viral infections, and different intervention strategies. It was held in Cairo, Egypt in collaboration with the International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France.

 

 

 

The Second PAEMS Conference (PAEMS’96) was held in Cape Town, South Africa from 23-25 January 1996. It had the following theme “Risk Assessment of Environmental Mutagens and Carcinogens“. Dr WFO N. ‎Marasas and his colleagues at the Medical Research Council in South Africa organized the conference under the auspices of the South Medical Research Council (MRC).

 

The Third International Conference of the Pan-African Environmental Mutagen Society was held in Harare, Zimbabwe during 1-5 March 1999. The theme of the meeting was “Susceptibility to Environmental Mutagens: Molecular, Epidemiological and Public Health Aspects”. The meeting was held at the University of Zimbabwe and was organized by PAEMS President-Elect, Dr. Julia Hasler and Dr. Y. S Naik.

 

 

The fourth international conference of the Pan African Environmental Mutagen Society on was held in Cairo, Egypt, 2-7 March 2003 at Dar El Diafa, Ain Shams University. The theme of the meeting was "Child Health and Environmental Mutagenesis". The meeting was organized in cooperation with Ain Shams University. Since the PAEMS is encouraging young scientists to be attracted to this important field, the PAEMS Officers decided to announce the creation of PAEMS Award for Young Scientists for Excellence in Environmental Mutagenesis Research, to encourage increased research in this field.

 

   

 

The objective of the conferences was focused on Child health and Environmental mutagens as an African Agenda for preventive research. Children, who are uniquely vulnerable to toxicants because of their delicate developmental metabolic processes and inherent disproportionately heavy exposure, are more endangered by from a polluted environment than adults. Also diseases that are triggered by mutagens require decades to develop and accordingly future generations are in real danger.                                                                                                                                                                                              

The attendance of scientists from different parts of Africa was a reflection to the importance of protecting children against environmental toxicant, which recently became a major challenge to modern societies. At the conference 150 scientist from different Continents in the World were gathered. African scientists were mainly from Egypt, South Africa, Sudan, Zimbabwe, Kenya, Mauritius, Morocco, Cameroon, Burkina Faso, Nigeria, Tanzania and Gambia. Scientists from outside Africa were from United Kingdom, Denmark, Greece, Poland, Bulgaria, Japan, Siberia, Portugal, Spain, Armenia, Lithuania, Yugoslavia, South Korea, France, Italy, Russia, USA, Germany, Brazil, Australia, Sweden and Kazakhstan. Non African scientists attended to share their ideas and exchange their knowledge in the field of genetic toxicology.

Egyptian Minister of Health attended the Opening Ceremony together with the President of Ain Shams University. The opening ceremony was followed directly by the scientific program that was divided into five main topics: Environment and childhood cancer, Antimutagens and Anticarcinogens, Environmental mutagenicity and carcinogenicity (retrospective and prospective human studies) Environmental mutagenicity and carcinogenicity (experimental studies), research towards prevention of hazard, miscellaneous topics.

Training and Practical Demonstration courses were organized to provide the latest practical information for upgrading technical skills of Molecular Biology Scientists in Egypt and African countries in the field of PCR, site directed mutagenesis, Recombinant plasmid DNA and Bioinformatics. Practical workshops were distributed over several laboratories within Ain Shams University in order to be able to allow the largest number of participants to benefit from the courses.

The Conference was supported by various funding sources including the SARBIO of Zimbabwe, International Association of Environmental Mutagen Society (IAEMS), Egyptian fund for cooperation with Africa (Ministry of Foreign Affairs), Ministry of Health and Population, Egyptian Ministry State of Environment, Egyptian Council for Childhood and Motherhood, GlaxoSmithKline Company, Egyptian International Pharmaceutical Industrial Company (EIPICO) Ram Chack company, Delta Company Egyptian International Centre for Import, Medica Lab Company and Arab Drug Company (ADCO).

 

 

 

The Pan African Environmental Mutagen Society Fifth International Meeting “PAEMS 2005”PAEMS 2005 will be held in Fès, Morocco, from the 24th to 26th of November 2005.

The Co-organizer of the conference was Sidi Mohamed Ben Abdellah University and the coordinator was Pr. Fatima-Zahra SQUALI. The meeting offered a forum to exchange information, ideas and knowledge on the environmental issues, and to develop new ideas and initiate regional and international collaborative programs in the field of environmental mutagenesis. The scientific program features internationally recognized experts who will participle in plenary lectures, symposia, workshops, continuing education sessions and debates. PAEMS2005 was divided into morning sessions with plenary lectures and symposia and afternoon sessions with workshops, Alexander Hollander training courses and study groups.

 

 

 

 

1-Focus Areas

o       Environment and nutritional status

o       Environment and childhood cancer

o       Environment and congenital malformation

o       Smoking and drug addition in children

o       Pharmaceuticals and childhood cancer

o       National Preventive Program

2-Biomolecules indicatory of environmental pathology

o       Biomarkers

o       Risk assessment and prevention of environment hazards

o       Low doses and thresholds of hazardous exposure

3- New Technologies and precocious detection

o       Gene-environment interaction and genetic susceptibility

o       Chromosomal sensitivity towards genotoxic agents

4- Bioethics and Biocomputer

5-Future Prospects in Africa

o       Priority setting

o       Priority Research

o       Policy in environmental health in Africa

o       Promoting the role of women scientists in research in Africa

6- Genetic Toxicology Training course

o       Genetic toxicology assays such the Ames test

o       Chromosome aberration test

o       Micronucleus test with molecular cytogenetics

 

 

The Sixth Conference, PAEMS2008, Cape Town, South Africa

 

 

 

  

FUTURE PROSPECTS

Preventing environmental health problems requires: (1) having adequate expertise and resources to investigate and respond to such diseases and injuries; (2) monitoring the population and its environment to detect hazards and to provide early warning signals for health problems; (3) monitoring the population and its environment to assess the effectiveness of prevention programs; (4) educating the public and select populations on the relationship between health and the environment; (5) ensuring that laws, regulations, and practices protect the public and the environment from hazardous agents; (6) providing public access to understandable and useful information on hazards and their sources, distribution, and health effects; (7) coordinating the efforts of all government agencies and non-governmental groups that are responsible for environmental health; and (8) providing adequate resources to accomplish these tasks. Development of additional methods to measure environmental hazards in people will permit more careful assessments of exposures and health effects.

 

Conclusion:

Despite the great efforts made to improve the situation, currently several actions are still required for environmental protection. There is a need for a standard and internationally available toxicological profile on all major man-made environmental chemicals. There is an equal need for both national and international coordination of human surveillance studies in cases where people are exposed to a known carcinogen or mutagen at levels considered likely to induce significant genetic effects. Finally, at the national level, it is necessary to consider the relative importance to human health of discrete chemical mutagen and carcinogens.

 

 

References

Abdel-Aziz, F., Habib, M., Mostafa, K. Abdel-Hamid, M., Gamil, F., Madkour, S., Nabiel, N.,Thomas, M.,  Fix, A.D., Strickland, T.,  Anwar, W. and  Sallam, I.; 2000. Hepatitis C virus (HCV) infection in a community in the Nile Delta: population description and HCV prevalence. Hepatology; 32:111-5.

Al –Saleh, I.A. 1994. Pesticides: a review article. J. Environ Pathol Toxicol Oncol 13:151-161.

Anwar, W.A., 1991. Cytogenetic Monitoring of Human Populations at Risk in Egypt: Role of Cytogenetic Data in Cancer Risk Assessment-Environmental Health Perspectives. Vol. 96 pp. 91-95.

Anwar, W.A., 1993. Mycotoxins as Mutagens and Carcinogens, The Proceedings of The First Pan African Environmental Mutagen Society Meeting, 23-26 January, 1993, Cairo, Egypt in African Newsletter on Occupational Health and Safety (Supplement 2).

Anwar, W.A., 1994. Assessment of Cytogenetic Changes in Human Populations at Risk in Egypt- Mutation Research 313: 183-191.

Anwar, W.A., 1997. Biomarkers of Human Exposure to Pesticides. Environmental Health Perspectives Supplements, Vol. 105 (Suppl. 4) 801-806.

Anwar, W.A., Gabal M.S., 1991. Cytogenetic Study in Workers Occupationally Exposed to Mercury Fulminate-Mutagenesis 6 :( 3) 189‑192.

Anwar, W.A., Ibrahim, S., Mostafa S., El Serafy, M., Hemida, S. A. and Hafez, A. S., 1994a. Chromosomal Aberrations and Micronucleus Frequency in Nurses Occupationally Exposed to Cytotoxic Drugs-Mutagenesis, 9 (4): 315-317.

Anwar, W.A., and Kamal A.M., 1988. Cytogenetic Effects in a Group of Traffic Policemen in Cairo Mutation Research, 208: 225‑231.

Anwar, W..A. and Shamy, M., 1995. Chromosomal aberrations, micronuclei and urinary thioethers in reinforced plastics workers exposed to styrene-Mutation Research, 327: 41-47.

Anwar, W.A., Sherif, M.R. Zaki, S., Eldin, S., Samir, M.H. Fikry, B., El-Bokl, F., 1994b. Cytogenetic Changes among Personnel Exposed to Anesthetic Gases-Egyptian Journal of Anesthesiology, 10 (1): 237-253.

Anwar, W.A., Sherif Abdel Rahman, Randa El Zein, Hosam M. Mostafa and William W. Au., 1996. Genetic Polymorphism of GSTM1, CYP2E1 AND CYP2D6 in Egyptian Bladder Cancer Patients-Carcinogenesis 17 (9): 1923-1929.

Anwar, W.A. and Wild, C.P., 1994. Meeting report of the First Pan African Environmental Mutagen Society meeting January, 1993, Mutation Research 312: 61-63.

Ashby, J., Anwar, W., Au, W.A., Massoud, A. and Gentile, J.M., 1993. Genetic Toxicology in Developing Countries: Comments and Recommendations. Environmental Health Perspectives Supplements, Vol. 101 (Suppl. 3) 335-338.

Au, W.W., Anwar, W.R. and Tennant, R.W., 1993. Environmental Mutagenesis in Human Populations at Risk.  Environ. Health Persp., 101, Suppl. 3, pp. 1 – 340.

Au, W. W. and Sram, R.J.  1996. Environmental Mutagens.  Environ. Health Persp. 104, Suppl. 3, pp. 421 – 690.

Au, W. W., Chulasiri, M., Kusamran, W., and Waters, M.D, 1999.  Understanding Gene and Environmental Interactions.  Mutat. Res., 428, 1 – 376 (40 manuscripts).

Au, W.W., Sierra-Torres, H., Cajas-Salazar, N., Salama, A. S., 1999a. Inheritance of polymorphic metabolizing genes on environmental disease and on quality of life.  Mutat. Res., 428, 131-140.

Au, W.W., Sierra-Torres, H., Cajas-Salazar, N., Shipp, B.K., and Legator, M.S., 1999b.  Cytogenetic effects from exposure to mixed pesticides and the influence from genetic susceptibility.  Environ. Health Persp., 107, 501-505.

Badawi AF, Michael MS., 1999. Risk factors for hepatocellular carcinoma in Egypt: the role of hepatitis-B viral infection and schistosomiasis. Anticancer Res. Sep-Oct; 19(5C):4565-9. 

Bedwani R, Renganathan E, El Kwhsky F, Braga C, Abu Seif HH, Abul Azm T, Zaki A, Franceschi S, Boffetta P, La Vecchia C., 1998. Schistosomiasis and the risk of bladder cancer in Alexandria, Egypt. Br J Cancer.  Apr; 77(7):1186-9. 

El Khoby T., 2000. Schistosomiasis in Egypt, Amer J Trop Med & Hygiene, volume 62:88-99.

Frank,C.,  Mohamed, M.K.,  Strickland, G.T.,  Lavanchy, D., Arthur, R,  Magder, L.S., El Khoby, T. Abdel- Wahab, Y,  Ohn,E.A,  Anwar, W., Sallam, I., 2000. The Role of Parenteral Antischistosomal Therapy in the Spread of Hepatitis C in Egypt. The LANCET, 355: 887-891, March.

Habib, M., Mohamed, M.K., Abdel-Aziz, F., Madger, L.S., Abdel-Hamid, M., Gamil, F., Madkour, S., Mikhail, N.N., Anwar, W., Strickland, G.T., Fix, A.D., Sallam, I., 2001. Hepatitis C virus infection in the Nile Delta: Risk factors for seropositivity, Hepatology,  33(1), 248-253.

Hicks, R. M.. 1982. Nitrosamines as possible etiological agents in bilharzial bladder cancer. In: Magee, P.N. (Eds).  Banbury Report No. 12: Nitrosamines and Human Cancer. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY pp. 455‑471.

Hirvonen, A., Watson, M.A., Bell, D.A.,. Mostafa, H.M., Anwar, W.A., 1996. Deficiency of GST Genes and Risk of Bladder Cancer and Schistosomiasis.  Cancer Detection and Prevention, Volume 20, issue 5, 3rd International Symposium "Impact of Cancer Biochemistry on Diagnostic and Prognostic Indicators in Predictive Oncology and Therapy", Nice, France - page 450. October 26-28.

Ibrahim, A.S. and Elsebai, I., 1983. Epidemiology of Bladder Cancer. In Elsebai I., ed., Bladder Cancer, Vol. I, Boca Raton, FL, CRC Press, pp. 17-38. International Agency for Research on Cancer (IARC), 1994. Monographs volume 61: Schistosomiasis, Liver Flukes and Helicobacter Pylori, Lyon, France 7-13 June.

International Agency for Research on Cancer (IARC), 1994. Monographs volume 61: Schistosomiasis, Liver Flukes and Helicobacter Pylori, Lyon, France 7-13 June.

Kietthubthew, S., Hutcha, S., Au, W.W.  Genetic and environmental interactions on oral cancer in southern Thailand.  Environ. Mol. Mutag., 37, 111-116, 2001.

NIEHS. 1997. Symposium on the Environmental Genome Project, National Institute of Environmental Health Sciences.

Rosin, M.P., and Anwar, W.A., 1992. Chromosomal Damage in Urothelial Cells from Egyptians with Chronic Schistosoma Hematobium Infections-International Journal of Cancer 51: 1‑5.

Rosin, M.P., Anwar, W.A. and Ward, A.J., 1994a. Inflammation, Chromosomal Instability and Cancer: The Schistosomiasis Model-Cancer Research Supplement 54, 1929s-1933s.

Rosin, M.P., Zaki, S.S., Ward, A.J. and Anwar, W.A., 1994b. Involvement of Inflammatory Reactions and Elevated Cell Proliferation in the Development of Bladder Cancer in Schistosomiasis Patients. Mutation Research 305: 283-292.

National Cancer Institute (NCI), 2003. Cairo University, Cairo, Egypt, Department of Biostatistics and Epidemiology, unpublished data 1975-2003, ().

National Cancer Registry Report, Ministry of Health and Population, Egypt, 2002.

Nafeh, M.A., Medhat, A., Shehata, M., Mikhail, N.H., Swifee, Y., Abdel-Hamid, M., Watts, S., Fix, A.D., Strickland, G.T., Anwar, W., Sallam, I., 2000. Hepatitis C Virus Infection in a Community in Upper Egypt: 1. Cross-sectional Survey.  Am J Trop Med Hygiene 63(5-6) 236-41.

Tricker, A. R., Spielhader, B. and Preussman, R, 1989. Environmental exposure to preformed N‑nitroso compounds and nitrosating agents in human cancer etiology. Pharmacogenetics, 2: 272‑277.

World Health Organization (WHO), 1997. Indicators for Policy and Decision Making in Environmental Health. Geneva, Switzerland: the Organization, June.

World Health Organization (WHO), 1997b. Fact Sheet 170, June.

World Health Organization (WHO) Report, 2001. Publications of the World Health Organization, Geneva.

Wild, C.P., Shrestha, S.M., Anwar, W.A. and Montesano, R., 1992. Field Studies of Aflatoxin Exposure, Metabolism and Induction of Genetic Alterations in Relation to HBV Infection and Hepatocellular Carcinoma in The Gambia and Thailand. Toxicology Letters, 64/65, 455-461.


Prof. Wagida Anwar, MD is a Professor of Community, Environmental and Occupational Medicine and Director of Ain Shams Center for Genetic Engineering and Biotechnology (ACGEB) at Ain Shams University, Cairo, Egypt. She is the  First recipient of the EMS-Hollaender International Fellow award, 2000. She was a fellow at Collegium Ramazini (Italy),   Adjunct Associate Professor in the Department of Preventive Medicine and Community Health, University of Texas,  Adjunct Professor, Medical School, University of Northumbria (UK), Chairperson of the Regional Advisory Panel (RAP) for Reproductive Health Research, WHO (Switzerland), Secretary General of the International Association of Environmental Mutagen Societies (IAEMS). In Egypt, she has served as the Former President of the Pan African Environmental Mutagen Society (PAEMS), the Secretary General  of the Egyptian Environmental Mutagen Society, a  Member of the National Environmental Research Council, National Academy of Scientific Research and Technology, National Committee of Genetics, National Academy of Scientific Research and Technology,  Member of the National Committee of Toxicology, National Academy of Scientific Research and Technology, Member of the Environment Committee, National Women Council,  Member of the Board of the General Federation of  Non-Governmental Organizations. Her email is wagidaanwar@yahoo.com
 



www.ambassadors.net
mail@ambassadors.net