Message from the President

Masayuki Mishima (2020-2021 The President of JEMS)

In our lives, we are exposed to increasing number of human-made chemicals. Some of them are mutagens--genotoxicants, that induce cancer-causing mutations and genetic alterations which can be passed on to the next generation. The Japanese Environmental Mutagen Society (JEMS) works to promote basic research into mutagens which exist in humans, the organisms around us, and the environments we live in, particularly those mutagens which have a significant impact on public health. In addition, we aim to disseminate information about mutagens and related technology. Our 50th annual meeting will be held in the autumn of 2021. Our official journal, Genes & Environment (G&E), achieved its first impact factor in 2020. These annual meetings and the publication of G&E are our most important academic activities. The culture of JEMS encourages frank discussion among members from diverse academic, regulatory, and industry backgrounds in order to accelerate progress in the investigation of genotoxic agents--their detection, identification, metabolism and underlying mechanisms--and to help establish and validate standard test methods. JEMS plays an important role in the establishment, implementation, and dissemination of various regulations on food additives, pesticides, environmental pollutants, pharmaceuticals, cosmetics, and occupational hazards.

Today, carcinogenic pollutants, food additives, pesticides, and other potential toxins are strictly controlled in Japan. However, new issues are emerging because of our increasingly globalized supply chains. At times, products are pulled from shelves after being contaminated by genotoxic agents from imported ingredients. Approximately half the population are diagnosed with cancer within their lifetime, and although advances in cancer therapy have increased the likelihood of survival, more attention is being paid to secondary carcinogenesis caused by genotoxic anti-cancer drugs. Even the normal cooking of food or our own intestinal bacterial flora can produce genotoxic chemicals. No matter how strict the regulations are on new chemicals in Japan, we can never truly free ourselves from genotoxic agents.

JEMS will add "genome" to its name after the 50th annual meeting. We intend to go beyond traditional research focusing on hazard identification to tackle emerging issues in a new era. What should genotoxicologists go from here? We need to quantitatively discuss genotoxic risk based on the complex dynamic between biology and exposure, instead of just asking whether something is genotoxic or not like we have in the past. We need to understand the many factors involved in human carcinogenesis and estimate their varying impacts, to improve QSAR systems so they can assess a multitude of chemicals, to investigate quantitative biomarkers of DNA damage, to understand the systems that repair DNA, and to elucidate epigenetic influences. We must also embark on new and as yet unknown paths of investigation. As genotoxicologists, we should assess the genomic stability of iPS cells designed for clinical applications, predict how the widespread use of genetically modified organisms will impact biological evolution, and propose recommendations on the appropriate use of genetic technology. We are not just adding a word, "genome", to the name of our society--we are opening the door to a new field of "genome toxicology", that explores how changes in genetic material influence the whole genome, and their ultimate effect on individuals and species.

Masamitsu Honma (2018-2019 The President of JEMS)

In the period of high economic growth in 1960s in Japan, the environment deteriorated due to rapid industrialization, causing serious pollution problems by industrial chemicals. In addition, to cope with the ever-increasing population, increased production of food is essential, and large amounts of pesticides and food additives were used. A class of chemical substances from environment or foods have a potential to cause cancer or genetic diseases. These are called "mutagens". The Japanese Environmental Mutagen Society (JEMS) was founded in 1972 for the purpose of promoting basic research into mutagens which exist in humans, organisms and the global environment. Our society is focusing on particular mutagens which have a crucial effect on public health. In addition, we aim to spread their reference information and technology. We will have the 47th JEMS annual meeting in Kyoto, November. JEMS has the oldest history among toxicology societies in Japan.

At the beginning of the establishment of JEMS, we mainly studied about identification of mutagenic pollutants in the environment, demonstration of mutagenicity of food additives and agricultural chemicals, discovery of new mutagenic substances in cooked foods, the metabolic activation mechanism of the environmental mutagens or carcinogen. Through these studies, many mutagenicity / genotoxicity test methods have been developed, and standardization and international guidelines of the test methods have advanced. In addition, the outcomes of the studies are reflected in laws such as the Chemical Substance Control Law and the Food Sanitation Act. Currently, health hazards due to ingestion of mutagenic substances through the environment and food are strictly regulated to be almost zero. This is exactly the result of the victory of regulatory science.

Meanwhile, the field of basic research also made great progress. The subject of mutagenicity is DNA / Genome. Advances in molecular biology, cell biology and cytogenetics have elucidated the mechanisms of DNA replication, repair, and recombination, and the advancement of analytical technology has made it possible to know the mechanism of toxicity of individual mutagenic chemical substances in detail. At present, we can analyze whole genome DNA sequence to identify mutations in a short period. This is the ultimate mutagenicity test, there is nothing better than this method. I feel that JEMS has conquered the serious mutagenic substances in our living environment through regulatory science and basic research. About 50 years since the establishment of JEMS, one era has ended now.

What should we do at the next era, JEMS? This is a major issue common to all scientific societies, not limited to JEMS. We must challenge new things beyond "Environment mutagens" by throwing out past ideas and methods. I said that we conquered the serious mutagenic substance in our environment. It may be conceit. Many new mutagens may exist in our surroundings, but it may just be impossible to see in the past method. Stick to the traditional ways and do not overlook new threats. A more sophisticated strategy is necessary.

At the end of 2017, the Japanese government started to formulate "Integrated Innovation Strategy" aiming for innovation of science and technology across fields. It supports research and development by setting priority fields such as health, medical care, and IT. In this trend, JEMS has to move new research challenges, and defeat new threats against human health.

Yoshifumi Uno (2016-2017 The President of JEMS)

 One of the concerns of the Japanese Environmental Mutagen Society (JEMS) is to assess the risk of chemical mutagens/genotoxicants. Many researchers developed simple assays to detect the mutagens/genotoxicants sensitively, i.e., mutagenicity/genotoxicity tests, and those methods are internationally standardized as guidelines for the testing of chemicals. A lot of JEMS members had and have greatly contributed to establishments and revisions of the test guidelines. Now most of new chemicals are evaluated with the mutagenicity/genotoxicity tests, and mutagens/genotoxicants are strictly regulated under laws on chemicals. Some of JEMS members also join national/international committees to regulate chemicals and make great effort to keep human health. JEMS members continue to report a lot of new findings that greatly contribute to regulatory science, and they discuss how they should evaluate the risk of mutagens/genotoxicants correctly based on the newly available data and its interpretation.

 We will welcome you to JEMS if you are interested in our activities!

Yasunobu Aoki (2014-2015 The President of JEMS)

I would like to say a few words on my inauguration as Chair of the Japanese Environmental Mutagen Society (or JEMS).

JEMS members have led the field of environmental mutagen research, as has been described in addresses by the JEMS Chairs over the years. I hope to draw on this research heritage to support further advances in environmental mutages research.

Humans and other organisms have flourished on Earth by responding adeptly to "environmental information," such as physical factors or chemical substances they receive from the environment, and by accurately passing on to successive generations the "genetic information," that is, the DNA base sequences recorded in the genes on their genomes. Living things take in various chemical substances from the environment through the atmosphere, water, or food, and are also exposed to radiation and solar rays. Many of the damaging effects of chemical substances or physical factors are reduced through defense mechanisms, but some of these substances or factors are mutagenic, causing genetic mutations that result in changes to the base sequence or other aspects of DNA structure. Chemical substances or physical factors that exhibit mutagenicity are termed mutagens. Recent research has shown that gene function can be modified through epigenetic effects, for example through changes to DNA methylation. Mutations in future generations can occur if such gene mutations or epigenetic effects occur in the reproductive cells. Gene mutations occurring in somatic cells can cause cancer. Some of the most important research in the life sciences, as well as the health sciences, is aimed at understanding such gene mutations, the mechanisms by which they affect gene function, and defense mechanisms against such mutations. I believe that the role of JEMS is to support efforts to understand the adverse effects (or genotoxicity) on these gene structures or functions. The key words "gene and environment interaction" describe the cross-talk between environmental information and genetic information. Our role is expressed by the JEMS motto "Science for Genome Safety" and the title of our English-language journal "Genes and Environment."

For most of the history of life, chemical substances and physical factors have been naturally occurring, but industrialization since the early 20th century has resulted in the use of more convenient man-made chemicals. Societies now release artificial mutagens into the environment. Because we tend to think of pollution as concluded issue, we have tended to give increasingly less consideration to the health impacts posed by the environment. But unidentified mutagens still exist and there may be numerous unidentified challenges ahead, as demonstrated by the recent classification of outdoor air pollution as an IARC Group 1 carcinogen (carcinogenic to humans). Research into environmental mutagens may be the bioscience of the 21st century.

From a health science perspective, it is important to identify mutagenic chemical substances or physical factors that people may be exposed to or ingest. We also need to evaluate the risks and demonstrate whether intake levels are within the safety margins. This is also a matter for regulatory science, where society intersects with natural sciences. JEMS has a significant role to play in these efforts.

The development of mutagenicity test methods for identification of mutagen and for basis of mutagenic risk assessment is a key aspect of securing safety. Test methods should not be developed by countries in isolation, but should be advanced through collaborative and harmonious efforts between countries. Test methods developed through the cooperation of JEMS members have been adopted for test guidelines of the OECD or ICH, the international body responsible for harmonizing pharmaceutical regulatory affairs. JEMS members have also participated in efforts to define test guidelines and have made significant contributions in this regard.

We have now entered an age when it is possible to sequence the entire genome of an individual, because of the increased use of next-generation DNA sequencers over the past few years. I expect new fields of environmental mutagen research to open up because of such advances in analytical technologies and genetic engineering. I also expect various unforeseen challenges to emerge in relation to science for genome safety, owing to the changes in society and human activities. Economically developing countries are experiencing the same environmental pollution problems that we experienced in Japan. Research by JEMS members is also helping to overcome these problems. JEMS is engaged in a wide range of activities involving mutagens, from basic biosciences to applied research on task solutions such as new test methods. These activities now involve close ties between academia, public research bodies, and industry. JEMS membership has well-balanced representation from all three sectors and much collaborative research is underway. In the future, we welcome the participation of researchers from related fields and hope to further our activities as a scientific body to support and promote research environmental mutagen research.

Hiroshi Kasai (2012-2013 The President of JEMS)

It is my great honor to be appointed as the president of the Japanese Environmental Mutagen Society (JEMS), which has 40 years of history. Since the Fukushima nuclear power plant accident, accompanying The Great East Japan Earthquake, many problems have arisen. As ionizing radiation is an environmental mutagen, we must continue our efforts in our responsibility as members of the JEMS.

The most important point is to stop the release of radioactive materials into the atmosphere and the marine environment. On the other hand, the neighbors of the Fukushima atomic power plant are concerned about accumulated radioactivity in the soil. As researchers, we need to confirm the following two items and release accurate information. 1) What part of the research data is scientifically conclusive and what part is not sufficiently clear? 2) Do people have access to correct, scientifically established information? We are living with a wide variety of environmental mutagens. Among the group 1 carcinogens (sufficient evidence of carcinogenicity in humans) identified by IARC that people frequently encounter, such as sunlight, cigarette smoke (main stream, side stream), and ionizing radiation, etc., sunlight and cigarette smoke are moderate concerns, depending upon individual opinions. However, ionizing radiation is now considered as an extremely dangerous agent, since the Fukushima accident. We should calmly realize that the radioactive materials released by the accident correspond to only part of the entire risk from a variety of environmental mutagens.

When I read the abstracts of the JEMS Annual Meeting from 30 years ago, I noticed that many researchers had studied the chemical components of mutagens in air, earth, river, foods, ink, hair dye, etc. Recently, research on gene mutations and toxicogenomics using modern technology has shown remarkable developments and is the predominant focus in the meeting abstracts. I think that in addition to these frontier fields, we should still continue chemical studies on environmental mutagens, because it is difficult to prevent cancer without identifying unknown mutagens. In 2007, we organized the first Asian Conference on Environmental Mutagens, in Kitakyushu, Japan. In the future, we need to collaborate especially with Asian countries, because we have many common subjects, such as yellow sand, photochemical smog, ocean pollution, and antimutagens in Asian foods. The purpose of environmental mutagen research is to defend humans from mutagens; therefore, it is important to conduct human biomonitoring studies on exposure to mutagens, including their absorption and excretion, as well as analyses of DNA adducts and gene mutations, using human blood, saliva and urine samples. It is also important to publish experimental data in a journal. "Genes and Environment" is the official journal of JEMS, and it covers environmental mutagenesis, toxicogenomics, epigenetics, risk evaluation, regulatory sciences, etc. I hope that many important papers will be submitted to this journal, to maintain its high scientific quality. Submissions from foreign researchers are welcome. Ideally, these research data will be useful for human health.

Dr. Takashi Yagi (2008-2009 The President of JEMS)

The Japanese Environmental Mutagen Society (JEMS) was founded in 1972 for the purpose of promoting basic research into mutagens which exist in humans, organisms and the global environment.Environmental mutagens are chemical or physical agents present in the environment that cause genetic variations regardless of inheritability.

Our society is focusing on particular mutagens which have a crucial effect on public health. In addition, we aim to spread their reference information and technology.

The research at the JEMS includes searches for unidentified mutagenic substances in foods, water and the atmosphere, measurement of mutagenic substances in the environment, elucidation of mutagenic and carcinogenic mechanisms in humans, elucidation of differences in mutagenic susceptibility among humans or animals, investigation of the complex effects of some mutagens, genotoxicity tests of foods, medicine and chemical materials, development and modification of genotoxicity tests, and carcinogenic risk evaluation of substances. The JEMS is also contributing to governmental plans such as determining safety standards for chemical issues and establishing standard genotoxicity tests. We have a long history of these studies and many eminent achievements, which contribute to human health. The JEMS is now making further efforts thanks to our brilliant predecessors. The study field is expanding from environmental influences, and molecular mechanistic study is developing based on the success of the human genome project.

The environment of Japan is polluted by numerous kinds materials to a low degree. It is said that the natural environment of Japan is cleaner because fewer people feel a smaller influence of environmental pollution on human health. However, according to a census of the National Cancer Center Institute, the age-adjusted cancer contraction rate has been unchanged or increased since 1975 for all types of cancer, except for stomach and uterus cancers. Compared to data in 1980 and 2000, we can see that the age-adjusted contraction rate of all cancers has been increasing among males after their 60s and among females after their 40s.

Most cancers are caused by environmental factors, and the increase in the cancer contraction rate is attributed to the change in the kind and amount of substances people take into their bodies (including natural materials in food), which are due to changes of lifestyle and surroundings. This hypothesis suggests that we should discuss the process of chemical carcinogenesis considering not only gene mutations caused by only chemicals but also other potential factors.

It is time to think about the disturbance of gene expressions in this field. We all know that mutagenicity and teratogenicity of chemicals were common mechanisms in human beings before the recent bloom of endocrine disturbance studies on chemical ligands of arylhydrocarbon and estrogen receptors. A mammalian cell has around 50 types of nuclear receptors, and their potential ligand substances exist in the environment. As chemicals work as agonists or antagonists, they suppress or promote transcription by an intrinsic ligand and its receptor.

For example, two functions of tamoxifen, which binds to estrogen receptor as a ligand and makes a DNA adduct, can be explained as cancer is caused by growth stimulation of tamoxifen-mutated estrogen-responsive cells. This process can be found in the hypothesis of the initiation and promotion of carcinogenesis, which have been known well for a long time. In some cases, the effect is by a substance such as tamoxifen, and in other cases, various substances have that effect in combination.

These are limitations in this field by working only on mutagenesis. If we want to try to clarify the total biological effects of environmental chemicals, we need to develop cutting-edge methods such as an exhaustive analysis of gene expression and affiliate with other societies in our related fields. Changes in biological characteristics caused by changes in gene expression by chemicals were originally called environmental variation. So It appears that environmental mutagens as the cause of environmental variation, especially epimutagens that cause epigenetic change in gene expression, are an object to study.

Another challenge of the JEMS is affiliating with Asian countries. The economic growth of Asian countries such as Korea, China and India, is significant, and environmental mutagen researches in such countries are expanding. The JEMS is a central member of the Asian Association of the Environmental Mutagen Society (AAEMS) and cooperates with the EMS in each Asian country to share ideas to stop the noxious effects of environmental pollution, which is now spreading rapidly in Asian countries. The JEMS official journal "Genes and Environment" is open to scientists of all countries and will be a common platform to discuss these issues.

Keiji Wakabayashi (2006-2007 The President of JEMS)

Research activities in JEMS have been declining gradually in the past 10 years since 1995. In this past decade, the completion of human genome sequencing has created a demand for more diversified research. The rapid advances in biological research also created unfocused research outcomes with less originality.

Chapter two of JEMS bylaws says "An objective of this society includes the promotion of basic research and distribution of related information and technology on mutagens in human, biological, and global environments, particularly for those with an important association with public health."

What is important to get our society refocused? This subject has been frequently discussed by JEMS's Committee for Future Planning, which is headed by the former president Takehiko Nohmi. Based on the discussions, the committee recommends the following points:

1 Extensive promotion of basic research concerning "gene-environment interaction", which is the principal of our society.

2 Change the language of the official journal of JEMS to English and spread research outcomes in our society internationally. (The first English issue of Genes and Environment was released in February 2006 by the contribution of the chief editor, Dr. Nagao and other editors.)

3 Improve the relationship between Asian Environmental Mutagen Societies and JEMS (the First Asian Conference on Environmental Mutagens will be held from 28th to 30th November 2007 in Kitakyushu.)

It is not well understood what environmental factors are responsible for carcinogenesis in human. However, in order to reduce the risk factors of carcinogenesis, it is important to elucidate these factors one by one in relation to their carcinogenic mechanism, and to take an overview on a wide variety of carcinogenic factors. There are many subjects to be solved with the main contribution by our society, such as identification of unknown mutagens/carcinogens in diet, atmosphere, and water, elucidation of their carcinogenic mechanisms, identification of endogenous carcinogenic factors, asbestos exposure and its mechanism for carcinogenesis, safety of new chemical products, individual susceptibility for carcinogenesis, and the real risks of environmental mutagens/carcinogens for human carcinogenesis. Asian countries such as Korea and China seem to have similar problems. I hope to build an active and progressive society with a common understanding and the help of society members.

Takehiko Nohmi (2004-2005 The President of JEMS)

Chemical exposure to humans, and its biological consequences, are major concerns in modern societies all over the world. JEMS is the primary society that promotes cutting-edge science to evaluate the potential genotoxicity of chemicals to humans. JEMS encourages research in various areas, including genomic and proteomic approaches to investigate gene- environment interactions.

Establishment of a scientific basis for risk evaluation of chemicals to the human genome is an important but challenging task in the 21st century. We are proud to be a part of this effort, and we look forward to working with you to accomplish this important task for human health.