REPORTS ON SEMINARS
Seminar on "Biochemical Epidemiology"
The seminar on "Biochemical Epidemiology" was held in Honolulu, Hawaii, February 10 through February 12, 1981. Organizers were Dr. Allen H. Conney, Department of Biochemistry and Drug Metabolism, Hoffman-La Roche, Inc., Nutley, New Jersey; and Dr. Susumu Nishimura, Biology Division, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo. There were 26 speakers, 14 from Japan, 1 from the United Kingdom, and 11 from the United States.
Epidemiologic studies have provided evidence that a majority of human cancer cases are caused by environmental factors and are thus preventable. On the other hand, the specific environmental factors involved in the causation of several of the cancers most frequently occuring in the United States and Japan have not been identified with certainty. Within the past decade, rapid progress has been made in our understanding of the basic mechanisms of action of initiating carcinogens and tumor promoters. In addition, highly sensitive and rapid methods for detecting potential environmental carcinogens have been developed.
The purpose of this meeting was to bring epidemiologists together with laboratory scientists to discuss possible areas of future collaborative studies in which biochemical and molecular methods are applied to epidemiologic studies in man. The discussions focused on the following major topics:
The discussions on the role of dietary factors highlighted the need for new laboratory assays that might detect specific dietary factors, or metabolites in urine, feces, or other body fluids, in view of the questionable reliability of dietary histories and the need to identify very specific components of the diet. The recent discovery of Dr. Takashi Sugimura and his colleagues, that highly potent mutagens can be formed during the broiling of fish, provides a striking example of potential dietary carcinogens. Discussions on the complexities of carcinogen metabolism highlighted the need for further assessing inter-individual variations in humans. The development of antibodies to specific carcinogen-DNA adducts was highlighted as a potentially useful tool in human studies since such tissue samples might provide a "dosimeter" of carcinogen exposure and metabolism. The possible roles of oxygen radicals and other forms of activated oxygen in carcinogenesis were discussed with particular relevance to halogenated hydrocarbons, vitamins, and dietary antioxidants. Highly sensitive methods of mass spectrometry and of combined liquid chromatography-mass spectrometry were presented. The ability of these methods to detect extremely small amounts of carcinogens in environmental samples and body fluids (i.e., breast fluid or semen) were discussed. The epidemiology and clinical findings related to T cell lymphomas that appear to occur in clusters of high incidence in certain prefectures in Japan were reviewed. Interestingly, these cases show an abnormality of chromosome 14. Possible contributing factors include a mosquito borne virus and filariasis. Discussions relating to tumor promotion included the effects of sacchrine on Concanavallin A agglutinability of rat bladder mucosal cells, the discovery of a specific membrane-associated receptor for the phorbol ester tumor promoters, and the discovery of a new highly potent class of tumor promoters that are naturally occuring indole alkaloids (teleocidin and Lyngbya-toxin).
The conference was extremely successful in bringing together individuals from diverse disciplines. Specific examples were discussed in which biochemical methods and various recently developed laboratory assays could be applied to epidemiologic studies aimed at identifying specific carcinogens in the human environment. Hopefully this conference will stimulate greater collaborative efforts in this area. Indeed, most of the participants agreed that this type of inter-disciplinary approach represented a powerful future direction in cancer epidemiology.
Seminar on "Inter species Correlations in Chemical Carcinogenesis"
This U.S.-Japan Cooperative Seminar was held March 19 to March 21, 1981 at the International Business Information Center in Tokyo. The conference organizers were Dr. Shozo Takayama, Cancer Institute, Toshima-ku, Tokyo; and Dr. Curtis C. Harris, Laboratory of Experimental Pathology, Division of Cancer Cause and Prevention, National Cancer Institute, Bethesda, Maryland.
There were 18 speakers: 11 from Japan, 1 from the United Kingdom, and 6 from the United States. (Seminar agenda and participants begin on page 15.)
A major objective of the U.S.-Japan Cooperative Cancer Research Program is "...to identify carcinogenic factors and clarify mechanisms with a view to providing a fundamental basis for the prevention of human cancer." In the area of carcinogenesis and cancer prevention, one of the central problems is related to the extrapolation of carcinogenesis data and mechanisms from experimental animals to the human situation. Extrapolation is made difficult by variations in the oncogenic effects of environmental carcinogens among animal species as well as variation among individuals within a species. Such variation may be particularly wide in outbred populations such as humans. Finally, within a single individual one may find variations in response to carcinogens among different tissues and within a tissue among different cell types.
The conference entitled "Interspecies Correlations in Chemical Carcinogenesis" focused on comparative investigations of carcinogen metabolism, mutagenesis, and carcinogenesis in different biological systems. Based on current information from laboratory and epidemiological studies, the qualitative and quantitative interspecies differences were discussed by the participants from Japan, the United States, and the United Kingdom. Presentations by the participants served as useful starting points for active discussions that continued throughout the conference. Anatomical, physiological, metabolic, and genetic factors among animal species were found to influence carcinogen susceptibility and tissue specificity. These factors were found to exert their influence at different steps in the multistage process of carcinogenesis. Wide quantitative differences in response to carcinogens were found at the molecular, cellular, tissue, and animal levels of biological organization. Much of the discussion was directed at the relationship between these responses and the susceptibility to cancer in the intact organism.
Possible interspecies differences with respect to the fidelity of DNA repair and tumor promotion were also considered. The participants raised new questions and clearly restated others. The availability of both in vitro model systems using cells and tissues from various animal species, and well-established animal models of most human cancers, provide cancer researchers with the experimental tools to answer many of these questions. Finally, cancer epidemiology and clinical pharmacogenetics should continue to provide cancer researchers with important clues for future investigation.
AGENDA
SEMINAR ON BIOCHEMICAL EPIDEMIOLOGY
Honolulu, Hawaii, February 10 to February 12, 1981
| Tuesday, February 10 INTRODUCTORY SESSION |
||
| 8:30- 8:40 am |
Introductory Remarks |
Allan Conney Susumu Nishimura |
| 8:40- 8:55 |
Metabolic Epidemiology: Perspectives and Challenges |
Ernst Wynder |
| DIETARY FACTORS BREAST AND COLON CANCER |
||
| Chairman: Ernst Wynder |
||
| 8:55- 9:20 | Breast Cancer in Japan |
Haruo Sugano |
| 9:20-9:30 |
Discussion | |
| 9:30-9:50 |
COFFEE |
|
| 9:50-10:15 |
Metabolic Epidemiology of Breast and Colon Cancer | Ernst Wynder |
| 10:15-10:25 |
Discussion |
|
| 10:25-10:50 | Epidemiological Investigations of the Possible Significance of Ingestion of Pyrolysates of Amino Acids and Proteins in Human Cancer | Masanori Kuratsune |
| 10:50-11:00 |
Discussion |
|
| 11:00-11:25 | Dietary Nitrate Intake and Nitrosamine Content in Blood | Takashi Yamada |
| 11:25-11:35 | Discussion | |
| 11:35-12:00 | General Discussion | |
| 12:00 pm | LUNCH | |
| METABOLISM AND DNA MODIFICATION |
||
| Chairman: Takashi Sugimura | ||
| 1:30- 1:55 pm | Individuality in Chemical Biotransformations and the Use of Drug Metabolism as an Indicator of Carcinogen Metabolism | Allan Conney |
| 1:55-2:05 | Discussion | |
| 2:05- 2:30 | Polymorphic Oxidation and Individual Cancer Risk | Jeffrey Idle |
| 2:30-2:40 | Discussion | |
| 2:40- 3:05 | Variation of Drug Metabolism in Experimental Animals and Chemical Carcinogenesis | Yoshiyuki Hashimoto |
| 3:05-3:15 | Discussion | |
| 3:15- 3:45 | COFFEE | |
| 3:45- 4:10 | Carcinogenesis Studies Using Cultured Human Epithelial Tissues and Cells | Curtis Harris |
| 4:10-4:20 | Discussion | |
| 4:20- 4:45 | DNA Adducts as Markers for Metabolic Activation and Radioimmunoassays for Carcinogen-DNA Adducts | Bernard Weinstein |
| 4:45-4:55 | Discussion | |
| 4:55- 5:20 | Oxidative Damage to DNA | Bruce Ames |
| 5:20-5:30 | Discussion | |
| 5:30 | General Discussion | |
| Wednesday February 11 CHEMICAL METHODS, CYTOGENETICS, AND DNA REPAIR |
||
| Chairman: James Cleaver | ||
| 8:30- 8:55 am | High Sensitivity Measurements and Structural Characterization | James McCloskey |
| 8:55-9:05 | Discussion | |
| 9:05- 9:30 | Functional Relationship Between Male Fertility Parameters and Toxic Substances | Ralph Dougherty |
| 9:30-9:40 | Discussion | |
| 9:40-10:10 | COFFEE | |
| 10:10-10:35 | New Isoaccepting tRNA Species that Specifically Appear in Tumor and Undifferentiated Cells | Susumu Nishimura |
| 10:35-10:45 | Discussion | |
| 10:45-11:10 | Assessment of Carcinogens by CytogeneticStudies | Sheldon Wolff |
| 11:10-11:20 | Discussion | |
| 11:20-11:45 | Xeroderma Pigmentosum Patients in Eygpt: Epidemiology and Biochemical Markers | James Cleaver |
| 11:45-11:55 | Discussion | |
| 11:5 5-12:30 | General Discussion | |
| 12:30 pm | LUNCH | |
| GASTROINTESTINAL AND OTHER CANCERS | ||
| Chairman: Susumu Nishimura | ||
| 2:00- 2:25 | Neoplastic Changes in Gastrointestinal Tract and Life Style | Takashi Sugimura |
| 2:25-2:35 | Discussion | |
| 2:35- 3:00 | Biochemical Abnormalities in Subjects at High Risk for Colorectal Cancer | Martin Lipkin |
| 3:00-3:10 | Discussion | |
| 3:10- 3:40 | COFFEE | |
| 3:40- 4:05 | Factors Present in Human Feces that Inhibit Activities of Mutagens | Hikoya Hayatsu |
| 4:05-4:15 | Discussion | |
| 4:15- 4:40 | Epidemiological Studies on Risk Factors of Children’s Cancer | Takeshi Hirayama |
| 4:40-4:50 | Discussion | |
| 4:50-5:15 | The Search for Serum Markers in a Cohort Study of Cancer | Abraham Nomura |
| 5:15-5:25 | Discussion | |
| 5:25 | General Discussion | |
| Thursday February 12 LYMPHOMA, BLADDER CANCER, AND MISCELLANEOUS TOPICS |
||
| Chairman: Martin Lipkin |
||
| 8:30- 8:55 am | Epidemiological Study on Carcinogenesis by Mustard Gas with Special Reference to the Determination of Serum Glycoproteins for Early Detection of Cancer | Yukio Nishimoto |
| 8:55-9:05 | Discussion | |
| 9:05- 9:30 | Epidemiology of Malignant Lynphomas in Japan | Suketami Tominaga |
| 9:30-9:40 | Discussion | |
| 9:40-10:10 | COFFEE | |
| 10:10-10:35 | Immunologic, Clinical, and Pathologic Characteristics of Japanese Lymphoid Malignancies | Masanori Shimoyama |
| 10:35-10:45 | Discussion | |
| 10:45-11:10 | Diagnosis of Precancerous Stages of Bladder Cancer by Biochemical Analysis | Tadao Kakizoe |
| 11:10-11:20 | Discussion | |
| 11:20-11:45 | Epidemiological Studies on Smoking and Cancer | Takeshi Hirayama |
| 11:45-11:55 | Discussion | |
| 11:55-12:30 pm | General Discussion | |
| 12:30 | LUNCH | |
| FACTORS AFFECTING MUTAGENESIS AND CARCINOGENESIS | ||
| Chairman: Haruo Sugano | ||
| 2:00- 2:25 pm | Metabolic Aspects of Comutagenic Action by Norharman | Minako Nagao |
| 2:25-2:35 | Discussion | |
| 2:35- 3:00 | In Vivo Skin Tumor Promotion by Dihydroteleocidin B, a New Potent.Tumor Promoter | Hirota Fujiki |
| 3:00-3:10 | Discussion | |
| 3:10- 3:30 | Recent Studies in the Mechanism of Action of Tumor Promoters and Their Relevance to Epidemiologic Studies | Bernard Weinstein |
PARTICIPANTS
JAPAN
Dr. Hirota Fujiki
Head, Section of Metastasis National Cancer Center Research Institute Tsukiji, Chuo-ku, Tokyo
Dr. Yoshiyuki Hashimoto,
Professor Department of Hygienic Chemistry Pharmaceutical Institute Tohoku University Aobayama, Sendai
Dr. Hikoya Hayatsu,
Professor Faculty of Pharmaceutical Sciences Okayama University Tsushima, Okayama
Dr. Takeshi Hirayama
Chief, Epidemiology Division National Cancer Center Research Institute Tsukiji, Chuo-ku, Tokyo
Dr. Tadao Kakizoe
Staff, Urology Division National Cancer Center Hospital Tsukiji, Chuo-ku, Tokyo
Dr. Masanori Kuratsune,
Professor Department of Public Health Faculty of Medicine Kyushu University Higashi-ku, Fukuoka
Dr. Minako Nagao
Section Head, Biochemistry Division National Cancer Center Research Institute Tsukiji, Chuo-ku, Tokyo
Dr. Susumu Nishimura
Chief, Biology Division National Cancer Center Research Institute Tsukiji, Chuo-ku, Tokyo
Dr. Masanori Shimoyama
Head, Section of Hematology National Cancer Center Hospital Tsukiji, Chuo-ku, Tokyo
Dr. Haruo Sugano,
Director Cancer Institute (JFCR) Kami-Ikebukuro, Toshima-ku,
Tokyo
Dr. Yukio Nishimoto,
Professor Department of Internal Medicine School of Medicine Hiroshima University Kasumi, Minami-ku, Hiroshima
Dr. Takashi Sugimura,
Director National Cancer Center Research Institute Tsukiji, Chuo-ku, Tokyo
Dr. Suketami Tominaga
Chief, Epidemiology Division Aichi Cancer Center Research Institute Chikusa-ku, Nagoya
Dr. Takashi Yamada
Senior Research Staff National Institute of Hygienic Sciences Kami-Yoga, Setagaya-ku, Tokyo
Dr. Michio Yamakido,
Lecturer Department of Internal Medicine Hiroshima University School of Medicine Kasumi, Minami-ku, Hiroshima
UNITED KINGDOM
Dr. Jeffrey Idle
Department of Biochemical and Experimental Pharmacology St. Mary's Hospital Medical School Norfolk Place London W2 1PG, England
UNITED STATES
Dr. Bruce Ames,
Professor Department of Biochemistry University of California Berkeley, California 94720
Dr. James Cleaver,
Professor Laboratory of Radiobiology University of California School of Medicine San Francisco, California 94122
Dr. Allan H. Conney,
Director Department of Biochemistry and Drug Metabolism Hoffmann-La Roche, Inc. Nutley, New Jersey 07110
Dr. Ralph Dougherty,
Professor Department of Chemistry Florida State University Tallahassee, Florida 32306
Dr. Curtis C. Harris,
Chief Human Tissue Study Section Laboratory of Experimental Pathology Division of Cancer Cause and Prevention National Cancer Institute Building 37, Room 3A07 Bethesda, Maryland 20205
Dr. Lawrence Kolonel
Director, Epidemiology Program University of Hawaii at Manoa 1236 Lauhala Street Honolulu, Hawaii 96813
Dr. Martin Lipkin
Associate Member Memorial Sloan-Kettering Cancer Institute New York, New York 10021
Dr. James A. McCloskey,
Professor Department of Medicinal Chemistry 311A Skaggs Hall University of Utah Salt Lake City, Utah 84112
Dr. Howard F. Mower
Professor of Biochemistry Cancer Center of Hawaii 1236 Lauhala Street Honolulu, Hawaii 96813
Dr. Abraham M.Y. Nomura
Associate Professor Epidemiology Program Cancer Center of Hawaii University of Hawaii 1236 Lauhala Street Honolulu, Hawaii 96813
Dr. Lawrence H. Piette,
Director Cancer Center of Hawaii University of Hawaii at Manoa 1997 East-West Road Honolulu, Hawaii 96822
Dr. I. Bernard Weinstein
Professor of Medicine and Environmental Sciences Columbia University College of Physicians and Surgeons New York, New York 10032
Dr. Sheldon Wolff
Professor of Cytogenetics Laboratory of Radiobiology University of California San Francisco, California 94143
AGENDA
SEMINAR ON INTERSPECIES CORRELATIONS IN CHEMICAL CARCINOGENESIS
Tokyo, Japan, March 19 to March 21, 1981
| Thursday, March 19 OFFICIAL OPENING |
||
| 9:00-9:10 am | Introductory Remarks | Shozo Takayama Curtis Harris |
| SESSION I | ||
| Chairman: Peter Magee | ||
| 9:10- 9:30 | Genetic and Environmental Control of Zenobiotic Metabolism | Elliott Vesell |
| 9:30-9:40 | Discussion | |
| 9:40- 9:55 | Variation of Metabolic Activation of Chemical Carcinogens Among Species, Different Cell Types, Individuals | Toshio Kuroki |
| 9:55-10:05 | Discussion | |
| 10:05-10:30 | COFFEE | |
| 10:30-10:50 | Metabolism of Chemical Carcinogens in Humans and Experimental Animals | Herman Autrup |
| 10:50-11:00 | Discussion | |
| 11:00-11:15 | Detoxication of Chemical Carcinogens in Different Animal Species | Nobuo Nemoto |
| 11:15-11:25 | Discussion | |
| 11:25-11:45 | Carcinogen-DNA Adducts in Humans and Experimental Animals | Dezider Grunberger |
| 11:45-11:55 | Discussion | |
| 11:5 5-12:15 pm | General Discussion | |
| 12:15- 2:00 | LUNCH | |
| SESSION II | ||
| Chairman: Shozo Takayama | ||
| 2:00- 2:15 | Species Specificity in Metabolic Activation of Chemical Carcinogens in Microbial Mutagenesis Assays | Taijiro Matsushima |
| 2:15-2:25 | Discussion | |
| 2:25- 2:45 | Interspecies Differences in Carcinogen Metabolism and Microsome-mediated Mutagenesis | Alexander Wood |
| 2:45-2:55 | Discussion | |
| 2:55- 3:20 | COFFEE | |
| 3:20- 3:35 | SCE-inducing Activity of Chemicals and Their Carcinogenic Potency to Humans | Atsushi Oikawa |
| 3:35-3:45 | Discussion | |
| 3:45- 4:30 | General Discussion | |
| Friday, March 20 SESSION III |
||
| Chairman: Curtis Harris | ||
| 9:00- 9:15 am | Metabolic Aspects of Species Differences in Carcinogenesis by Dialkylnitrosamines | Masataka Mochizuki |
| 9:15-9:25 | Discussion | |
| 9:25- 9:40 | Autoradiographic Study of DNA Repair Synthesis in Tracheal Epithelium in Organ Culture, with Special Reference to DNA Repair Levels and Species Differences | Takatoshi Ishikawa |
| 9:40-9:50 | Discussion | |
| 9:50-10:20 | COFFEE | |
| 10:20-10:35 | The Difference of Stomach Cancer Incidence Induced by N-methyl –N’-nitro-N-nitrosoguanidine Among Various Strains of Rats | Oichiro Kobori |
| 10:35-10:45 | Discussion | |
| 10:45-11:05 | Skin Tumor Initiation and Promotion: A Comparative Study on Several Stocks and Strains of Mice | Thomas Slaga |
| 11:05-11:15 | Discussion | |
| 11:15-12:00 | General Discussion | |
| AFTERNOON | Informal Discussion | |
| Saturday, March 21 SESSION IV |
||
| Chairman: Takashi Sugimura | ||
| 9:00- 9:15 am | Use of Athynic Nude Mice for the Study of Carcinogenesis in Human Bronchus | Yukio Shimosato |
| 9:15-9:25 | Discussion | |
| 9:25- 9:45 | Susceptibility of Non-human Primates to Chemical Carcinogens |
Richard Adamson |
| 9:45-9:55 | Discussion | |
| 9:55-10:30 | COFFEE | |
| 10:30-10:50 | Interspecies and Organ-specific Susceptibility to N-nitrosamines | Peter Magee |
| 10:50-11:00 | Discussion | |
| 11:00-11:15 | Species Differences in the Induction of Tumors in the Liver and Urinary Bladder Following the Administration of Various Chemical Carcinogens | Shoji Fukushima |
| 11:15-11:25 | Discussion | |
| 11:25-11:45 | In Vitro and In Vivo Studies of Human and Animal Bladder Carcinogens | Marian Hicks |
| 11:45-11:55 | Discussion | |
| 11:5 5-12:15 pm | General Comments | Takashi Sugimura |
| 12:15-12:25 | Discussion | |
| CLOSING REMARKS | Curtis Harris | |
PARTICIPANTS
JAPAN
Shoji Fukushima
First Department of Pathology School of Medicine Nagoya City University l Kawasumi, Mizuho-cho Mizuho-ku, Nagoya 467
Takatoshi Ishikawa
Department of Experimental Pathology Cancer Institute l-37-1, Kami-Ikebukuro Toshima-ku, Tokyo 170
Oichiro Kobori
First Department of Surgery Faculty of Medicine University of Tokyo 7-3-1, Hongo Bunkyo-ku, Tokyo 113
Toshio Kuroki
Department of Cancer Cell Institute of Medical Sciences University of Tokyo 4-6-1, Shirokanedai Minato-ku, Tokyo 108
Taijiro Matsushima
Department of Molecular Oncology Institute of Medical Sciences University of Tokyo 4-6-1, Shirokanedai Minato-ku, Tokyo 108
Masataka Mochizuki
Tokyo Biochemical Research Institute 3-41-8, Takada Toshima-ku, Tokyo 171
Atsushi Oikawa
Department of Pharmacology Research Institute for Tuberculosis, Leprosy, and Cancer Tohoku University Seiryo-machi, Sendai 980
Yukio Shimosato
Pathology Division National Cancer Center Research Institute 5-1-1, Tsukiji Chuo-ku, Tokyo 104
Takashi Sugimura,
Director National Cancer Center Research Institute 5-1-1. Tsukiji Chuo-ku, Tokyo 104
Shozo Takayama,
Vice Director Cancer Institute 1-37-1, Kami-Ikebukuro Toshima-ku, Tokyo
UNITED KINGDOM
R. Marian Hicks
Department of Cell Pathology The Middlesex Hospital Medical School Riding House Street London, W1P 7LD
UNITED STATES
Richard H. Adamson,
Director Division of Cancer Cause and Prevention National Cancer Institute Bethesda, Maryland 20205
Nobuo Nemoto
Department of Experimental Pathology Cancer Institute 1-37-1, Kami-Ikebukuro Toshima-ku, Tokyo 170
Herman N. Autrup
Laboratory of Experimental Pathology Division of Cancer Cause and Prevent ion National Cancer Institute Bethesda, Maryland 20205
Dezider Grunberger
Division of Environmental Sciences and Institute of Cancer Research Columbia University College of Physicians and Surgeons New York, New York 10032
Curtis C. Harris
Laboratory of Experimental Pathology Division of Cancer Cause and Prevent ion National Cancer Institute Bethesda, Maryland 20205
Peter Magee,
Director Fels Research Institute Temple University Philadelphia, Pennsylvania 19140
Thomas Slaga
Biology Division Oak Ridge National Laboratory Oak Ridge, Tennessee 37830
Elliot S. Vesell
Department of Pharamacology Pennsylvania State University College of Medicine Hershey Medical Center Hershey, Pennsylvania 17033
Alexander Wood
Department of Biochemistry Drug Metabolism Hoffmann-La Roche, Inc. Nutley, New Jersey 07710