REPORTS ON SEMINARS

(1) Seminar on "Multiple Primary Neoplasms"

The seminar was held at the Oiso Prince Hotel, Oiso, Kanagawa, Japan, on February 17 and 18, 1983. The organizers were Dr. Curtis C. Harris, National Cancer Institute, U.S., and Dr. Keiichi Suemasu, National Cancer Center Hospital, Japan. There were 18 speakers: 7 from the United States and 11 from Japan.
In the opening address, Dr. Takashi Sugimura emphasized the importance of observations made by clinicians and pathologists of multiple primary cancers, mostly double cancers, in the single patient. Such observations are now more frequent, perhaps because of the prolonged survival of patients who have been cured of their primary cancer. Dr. Sugimura also noted the sentinel role of research-oriented clinicians in initiating investigations that have led to new insights into the mechanisms of carcinogenesis.
Incidence of multiple primary cancers at the time of autopsy is generally reported to range from 2% to 10%. Dr. Shaw Watanabe reviewed data from 5,456 autopsy cases at the National Cancer Center Hospital during the period from 1962 to 1982; 5.4% were double neoplasms, and 1.1% were triple (or more) neoplasms. The relationship among organs with multiple primary cancers was analyzed. After a primary oropharyngeal cancer, the incidence of second esophageal, gastric, or colon cancer was significantly increased. Other interesting temporal associations were a first esophageal cancer followed by a second gastric cancer, a first gastric cancer followed by a second colon cancer, and a first colon cancer followed by a second colon cancer. Such cases of multiple cancers could provide important indicators of cancer families and sources of human tissue specimens for laboratory investigation.
Dr. Satoshi Ebihara reviewed the case histories of 2,541 patients with head and neck cancer seen at the National Cancer Center Hospital between 1962 and 1977. Multiple primary cancer developed in 123 of these patients; 6 patients had three or more primary cancers. Primary head and neck cancers were most frequently followed by second cancers of the stomach, head and neck, lung, esophagus, or colon. One remarkable patient developed four primary cancers in the radiation field for treatment of acne, which suggests a genetic predisposition for radiogenic cancer.
Dr. Arthur Upton continued the discussion of radiation-induced cancer. Oncogenic susceptibility varies among Individuals and among different tissue sites in a single individual. Well-known examples of genetic predisposition to radiogenic cancer, including xeroderma pigmentosum, retinoblastoma, and nevoid basal cell carcinoma syndrome, were noted. The preferential localization of basal cell carcinoma at the scalp line, and not in the area of highest dose of radiation, in children treated for tinea capitis suggests a synergism between ionizing and non-ionizing (ultraviolet light) radiation in the sun-exposed areas.
Drs. Kyosuke Ushio and Martin Lipkin discussed multiple colorectal cancer. At the Japanese National Cancer Center Hospital, a review of the case histories of 89 patients with multiple colorectal cancers revealed that patients with a family history of intestinal cancer had their primary cancer diagnosed at a younger age, and that they had a higher tumor incidence in the ascending colon and cecum when compared to patients with a single cancer. The cumulative incidence of colorectal tumors in Japanese patients with a family history of colorectal cancer and/or malignancy of other organs was in close agreement with results reported in the United States.
A registry of individuals with high risk of cancer of the large intestine has been established at Memorial Sloan-Kettering Cancer Center. Dr. Lipkin reviewed reports suggesting that cancer of the large intestine was associated with increased frequencies of breast and endometrial cancer in the general population. He also described laboratory tests, including autoradiographic measurements of abnormally high proliferative activity of the colonic epithelial cells, that are being developed to improve the early identification of cancer-prone people. In laboratory studies, cultured adenoma cells are also being used to study the effects of putative tumor promoters.
The survival rate for children with cancer has much improved in recent decades, while the incidence of multiple primary cancers has increased. Dr. Tohru Ise described 34 cases of multiple primary childhood cancers; half of these cases had known genetic conditions that predispose to malignancy, e.g., hereditary retinoblastoma. Dr. Robert W. Miller discussed the role of the alert clinician in detecting the genetic and environmental origins of multiple primary tumors in children. He also noted that inheritance may have pleiotropic effects and that certain congenital abnormalities occur in association with childhood cancers.
It is predicted that deaths due to lung cancer, the most prevalent cause of cancer mortality in the United States, will soon surpass deaths due to stomach cancer in Japan. Dr. Ryosuke Tsuchiya found that 5.6% of the 1,334 patients treated at the National Cancer Center Hospital had multiple primary neoplasms; 66 patients had double cancers, and 9 had triple cancers. Although no "lung cancer families" were discovered in this group of patients, the double lung primary cancers were considered more likely to be found in occupational groups exposed to respiratory carcinogens, e.g., six patients were chromium platers.
Dr. Curtis Harris discussed the major determinants of lung cancer risk. Since the dominant etiological factor is tobacco smoke, the majority of the multiple cancers found in patients with lung cancer are at tissue sites (e.g., buccal mucosa, larynx, bladder, and esophagus) that are also known to be susceptible to the carcinogenicity of tobacco smoke. Genetic and acquired host factors also play an important role in the risk of multiple cancers. Using a questionnaire to survey the patient population with hematological malignancies in 53 Japanese medical oncology services, Dr. Kazumasa Yamada uncovered 222 cases of multiple primary cancers. In 77 cases, primary carcinoma was followed by hematological malignancies, 57% of which were acute leukemia. These secondary leukemias were generally granulocytic, with low rate of remission and a survival period of only a few months. The median time interval between first primary carcinoma and leukemia was 5 years in 26 patients who had received radiotherapy (median dose 6,000 rads).
Drs. Frederick Hecht and Barbara Kaiser-McCaw Hecht reviewed host factors that predispose to leukemia and/or lymphoma. They also reviewed recently published papers reporting the localization of cellular oncogenes to various human chromosomes that suggest the repositioning of cellular oncogenes by chromosomal rearrangements leading to oncogene activation.
Although breast cancer is one-fifth as frequent in Japan as in the United States, after a Japanese woman develops a primary breast carcinoma, her risk of a second breast cancer is equal to the risk in American females. Dr. Fujio Kasumi reported that bilateral breast carcinoma (157 cases) was the most frequent form of multiple primary cancer in 4,777 females with breast carcinoma. Family history of breast cancer and other well-known risk factors for bilateral breast cancer were similar to those identified in the U.S. population.
Dr. Nicholas Petrakis reviewed the U.S. data concerning multiple primary cancers associated with breast cancer. Women with a primary breast cancer have a threefold to fivefold increased risk of cancer in the contralateral breast. They also have an increased risk of ovarian cancer and, as some studies have suggested, an increased risk of endometrial or colonic carcinoma.
The last topic of the workshop, multiple endocrine neoplasia, was discussed by Drs. Kaoru Abe and R. Neil Schimke. Dr. Abe reviewed 10 patients with type I syndrome, i.e., tumors primarily of the pancreas, parathyroid, and pituitary, and 32 patients with other combinations of multiple endocrine tumors. In 8 of 10 patients with type 1 syndrome, the pancreatic tumors were multiple and associated with microadenomatosis and/or islet cell hyperplasia. These data indicated that such patients should be treated differently from those without type I multiple endocrine neoplasia. Dr. Schimke reviewed the salient clinical features and laboratory findings of the three, or perhaps four, types of multiple endocrine neoplasia syndromes. He also emphasized that these neoplasms were not neural crest in origin and that the basic gene defect and chromosomal abnormalities were essentially unknown.
During the concluding remarks, Dr. Curtis Harris emphasized points brought out during the extensive and fruitful discussion of the individual papers. Patients with multiple primary cancers are generally those who are unusually susceptible to acquired or hereditary host factors or who are exposed to high levels of environmental Garcinogens. These patients may also be probands of cancer families, so that a thorough inquiry of family history is of obvious importance. Numerous opportunities for combined laboratory-epidemiology studies of these patients were identified by the participants. For example, cytogenetic analysis, coupled with the recent developments in oncogene research, studies of DNA repair, or measurements of carcinogen-DNA adducts by highly sensitive enzyme radioimmunoassay, may lead to increased understanding of mechanisms and provide indicators of individual cancer risk.

(2) Seminar on "New Etiology of Lung Cancer"

A U.S.-Japan Cooperative Seminar on "New Etiology of Lung Cancer" was held at the East-West Center, Honolulu, Hawaii, March 21-23, 1983. The organizers were Drs. H.S. Rosenkranz, Case Western Reserve University, Cleveland, Ohio; E. Wynder, American Health Foundation, New York, New York; and T. Hirayama, National Cancer Center Research Institute, Tokyo. The meeting was opened by Dr. R. Adamson, U.S. National Cancer Institute, who introduced the underlying theme of the meeting.
Passive Smoking
Dr. S. Tominaga presented characteristics of lung cancer and its etiology in Japan. He stated that lung cancer is sharply increasing in all age groups among both sexes in Japan. The large increase in adenocarcinoma is particularly noteworthy. Both case-control studies and a cohort study on lung cancer, conducted in Japan, showed a lower relative risk from cigarette smoking (2 to 4), compared with the United States, where it is 10 to 20. Related problems, including features of active and passive smoking, air pollution, indoor pollution resulting from heating and cooking, and the possible role of diet, were reviewed.
Dr. T. Hirayama presented recent results of an ongoing large-scale cohort study in Japan on the relationship of passive smoking to lung cancer. The risk of developing lung cancer in nonsmoking women increased in proportion to the quantity of cigarettes their husbands smoked. These results are in accordance with a Greek study but somewhat at variance with an American Cancer Society study in the United States. Results similar to those of some studies on active smoking showed that the daily intake of green-yellow vegetables (rich in beta-carotene) lowered risk related to passive smoking. Dr. Hirayama suggested that this may be a human example of a promoter-inhibitor interaction model.
Dr. E. Wynder described the epidemiology of passive inhalation, reviewing existing evidence as well as uncertainties. He stressed the strong need for common use of standardized questionnaires for case-control studies; he also emphasized the need for standard criteria of pathological classification in order to compare results obtained in different communities and countries.
Dr. D. Hoffmann and Dr. H. Matsushita introduced their studies on indoor pollution related to tobacco smoke with special reference to its formation, analysis, and uptake. Most of the chemicals, including carcinogens, were found in higher concentration in sidestream smoke than in mainstream smoke. The fact that nicotine and cotinine have different half-lives in saliva, blood, and urine following exposure to passive smoking was stressed. The possibility of endogenous formation of nitrosamines in relation to inhalation of component chemicals by passive smoking was also suggested.
Dr. H. Kasuga described in detail his studies on passive smoking and urinary hydroxyproline. The ratio of urinary hydroxyproline to urinary creatinine (HOP ratio) in schoolchildren and their mothers was closely correlated to the fathers' (husbands') smoking habits. He suggested that elevated HOP ratio is due to lung tissue damage, especially damage to collagen and elastin, as a result of the prolonged inhalation of toxic substances in sidestream smoke. The group agreed that such studies should also be conducted in the United States.

Nitroarenes

The identification and measurement of nitroarenes in diesel emissions and in air samples in both countries were described by Drs. D. Schuetzle and H. Matsushita. The relative contributions of mononitropyrenes and dinitropyrenes were compared regarding direct-acting mutagenicity and amounts in diesel exhausts. Metabolism and biological properties of nitroarenes were discussed by Drs. H. S. Rosenkranz, Y. Onishi, T. C. Pederson, and F. A. Beland with special reference to the importance of nitroreduction in the metabolic activation of nitropyrene. Problems related to short-term and long-term bioassays were reviewed by Drs. J. Lewtas, R. O. McClellan, and J. J. Vostal. Dr. C. M. King reported that the 1-nitropyrene (1-NP) induced tumors at the injection site in DC rats and produced mammary tumors in female rats; in contrast, Dr. H. Tokiwa found that 1,6-dinitropyrene induced tumors at the injection site in male BALB/C mice, but that 1-NP was not tumorigenic. Dr. M. Terada showed mutagenicity of DNP using mammalian cells. He also reported that injection-site tumors occurred in F344 rats treated with 1,3-and 1,8-DNP, but that l-NP failed to induce tumors.
On the basis of available laboratory and epidemiological information, attempts at cancer risk assessment were made by Drs. R. E. Albert and I. T. T. Higgins. Dr. Albert presented an analysis of the lung cancer risk to humans from diesel emissions, employing the comparative potency approach. For the vehicle engine displaying the greatest mutagenic characteristics, the lifetime risk of lung cancer was estimated at four per ten thousand; for the lowest of the engines, the risk was estimated at two per million.
Dr. Higgins reviewed epidemiologic studies related to two questions: the effect of general air pollution on lung cancer rates, and the effect of environmental exposure to diesel emissions on lung cancer rates.
Possible effects of general air pollution have been suggested by urban-rural differences in lung cancer rates and by the presence of identifiable atmospheric mutagens. One study has suggested a reverse association between lung cancer rates and the proportion of sunny days per year in various cities. Other studies indicating a relationship between atmospheric pollution and lung cancer indicate higher rates of lung cancer in British migrants to countries with lower pollution than in natives of those countries. Furthermore, the older the migrants, the higher the rates. In the United States, urban rates exceed those of rural areas even after adjustment for cigarette smoking.
However, in each of these studies there exists a potential for one or more confounding biases, which may account for the results in the light of other negative studies. A 20- to 25- year followup of the British physician lung cancer study has shown no urban excess, and in a U.S. study in which urban-rural residence was controlled, occupation indicated no difference. Thus, the question remains unsettled, but it is unlikely that a major effect exists.
Dr. Higgins also reviewed the well-known studies of diesel-exposed workers. Studies from Los Angeles indicated that men occupationally exposed to diesel emissions exhibited an approximately 50% increase in the standardized lung cancer mortality ratio. A study employing data obtained from the United Mine Workers indicated a slight (10-15%) increase in lung cancer, but there was no evidence of a difference between diesel- and non-diesel-exposed miners. Potash miners did not differ from other U.S. populations in lung cancer incidence, and there was no relationship to employment in diesel-exposed miners. With a short followup period, Baltimore and Ohio Railroad employees experienced no variation in lung cancer rates associated with different occupational categories. Review of mortality figures for the Teamsters Union (truckers, mostly diesel) showed a slight increase in lung cancer mortality, but the data could not be controlled for other confounding variables, such as smoking and urban-rural residence. The well-known studies of London transport workers; including the more recent followup, cannot be interpreted as supporting a relationship between diesel exposure and lung cancer.
More recently, preliminary results of two U.S. studies suggest a positive association. Data for men occupationally exposed to diesel emissions in the heavy construction industry show less than expected mortality from all causes, but a possible increase in lung cancer death rates was noted. Additional data from the Railroad Retirement Board indicate a standardized mortality ratio of 142 for lung cancer; for individuals believed to be heavily exposed to diesel engines the ratio is 277. Unfortunately, the latter group may also have experienced greater exposure to asbestos. Furthermore, it may not be possible to control for smoking history.
Dr. Higgins believes that the effect of general atmospheric pollution on lung cancer rates is minor at worst, and that the effect of exposure to diesel emissions is not as yet established. He concluded by advocating enhanced efforts in two types of epidemiologic studies: cohort studies of groups with laboratory or otherwise certified exposure to diesel emissions, and case-control studies of lung cancer patients with careful ascertainment of past environmental/occupational exposures.
In summary, passive smoking and nitropyrenes, two recent developments in the etiology of lung cancer, were fully discussed. The need for bilateral and multidisciplinary collaboration, particularly strengthening exchange of information, materials, and personnel, to enhance research efficiency in both fields became apparent. A suggestion was made to establish two task groups in both countries, one concerning passive smoking and the other concerning nitroarenes and diesel emissions, to serve as a conduit for new information and to encourage joint projects.

(3) Seminar on "Carcinogenesis and Environmental Factors"

This seminar was held on March 28 and 29, 1983, at the Endicott House of the Massachusetts Institute of Technology in Dedham, Massachusetts. The organizers were Drs. Steven R. Tannenbaum and Gerald N. Wogan of the Massachusetts Institute of Technology, Cambridge, and Drs. Takashi Sugimura and Shigeaki Sato of the National Cancer Center Research Institute, Tokyo. There were 19 speakers: 11from the United States and 8 from Japan. The aim of the seminar was to discuss and exchange recent information on carcinogens and tumor promoters present in our environment, human exposure to these chemicals, results of animal carcinogenesis experiments with some newly found chemicals, and endogenous formation and metabolism of carcinogens and their modifiers.
The seminar was divided into three sessions: I. Analysis and Detection of Carcinogens and Promoters; II. New and Old Carcinogens and Promoters; and III. Modulation of Carcinogenesis. At Session I, recent methodology for detection and quantification of carcinogen adducts in biological materials, such as those using specific antibodies of postlabeling, was discussed. Covalent adducts of carcinogens with proteins such as hemoglobin were introduced as a means of measuring exposure of some workers to carcinogens. Also discussed were new methods for detecting probable bladder carcinogens and promoters by using con A-agglutination of bladder epithelial ceils, and for detecting tissue-specific carcinogens by measuring the incorporation of H-thymidine radioactivity during unscheduled DNA synthesis by various tissues obtained from rats treated with test chemicals. A study of the role of 0⁶-methylguanine (0⁶MeG) in mutagenesis was performed using the tetranucleotide containing 0⁶MeG, which was inserted into E. coli phage M13p8. Transfection of this vector into E. coli served as a marker to assay the GC to AT base-pair substitution by using resistance to Pst I endonuclease digestion. The mutation frequency was 10% in cells lacking the ability to remove this lesion, compared to 0.3% in cells with normal repair capacity.
A new method for detecting tumor promoters by their inhibition of EGF-induced tyrosine phosphorylation of EGF receptor by EGF was introduced. In this work, monoclonal anti-phosphotyrosine antibody coupled to Sepharose 4B was shown to work very efficiently in isolating tyrosine-phosphorylated EGP receptor from the crude cell extract. TPA and other classes of new tumor promoters, such as the indole alkaloids teleocidin and lyngbyatoxin and the polyacetates aplysiatoxin and debromoaplysiatoxin, all were found to inhibit tyrosine phosphorylation by EGF, but non-tumor-promoting analogs were not. Along with this new method, some recently detected mutagens in coffee (e.g., diacetyl compounds) and premutagens in soy sauce (e.g., l-methyl-1, 2, 3, 4-tetrahydro-beta-carboline-3-carboxylic acid and tyramine) were described.
In Session II, nitrosamines such as N'-nitrosonornicotine or 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone, specifically found in cigarette smoke condensate, and their metabolism were discussed. The metabolism of benzo(a)pyrene (B(a)P) in an established human lymphoblastoid cell line containing mixed function oxidase was also presented. Metabolism and DNA adduct formation of aromatic amines and nitroaromatic hydrocarbons were discussed. New types of mutagens, such as hydroxymethylfurfural, epsilon-(2-formyl-5-(hydroxymethyl)pyrrol-1-yl)-norleucine and 2-methyithiazolidine, were reported to be present in Maillard reaction products. Also reported was definite carcinogenicity, in mice and rats, of mutagenic heterocyclic amines originally isolated from various pyrolyzed materials, as well as carcinogenicity of dinitropyrenes in rats, were reported. The detailed results of carcinogenicity tests with 29 compounds for the past 8 years, conducted under the support of the Ministry of Health and Welfare of Japan, were presented and discussed.
Session III included a discussion on the usefulness of human tissue explants for studying metabolism of various types of carcinogens and for evaluating both the risk to humans of carcinogens and the microdetection method for mycotoxins and their adducts in biological samples. Very few environmental carcinogens, having three or more fused aromatic rings, were shown to be efficiently concentrated and purified by the use of "blue cotton," a cotton bearing a covalently bound copper phthalocyanine derivative. Results of experiments on ¹⁵N0₃- ingested into human bodies were presented in relation to formation of nitrosoproline. Urinary nitrosoproline was shown to have three distinct origins: a preformed dietary component; a component enriched in ¹⁵N from administered ¹⁵NO-; and a component independent of administered ¹⁵N0₃-. The presence of nitrosothioproline and nitrosomethylthioproline in human urine was reported by a Japanese group and an American group.
Discussions among American and Japanese researchers, held throughout the seminar and at other occasions, were mutually informative and beneficial for further studies of environmental factors in human carcinogenesis. It was regretted that Dr. Takashi Sugimura, one of the organizers of this seminar, could not participate due to illness; his paper was presented by his colleagues Dr. Minako Nagao and Dr. Shigeaki Sato.


SEMINAR AGENDA AND PARTICIPANTS

(1) SEMINAR ON MULTIPLE PRIMARY NEOPLASMS
Oiso, Japan, February 17-18, 1983

AGENDA

PARTICIPANTS

UNITED STATES
Dr. Curtis C. Harris
Laboratory of Human Carcinogenesis
Carcinogenesis Intramural Program
Cancer Cause and Prevention
National Cancer Institute

Dr. Frederick Hecht
The Genetics Center and Cancer Center
Southwest Biomedical Research Institute

Dr. Martin Lipkin
Gastrointestinal Cancer Research
Memorial Sloan-Kettering Cancer Center

Dr. Robert W. Miller
Clinical Epidemiology Branch
National Cancer Institute

Dr. Nicholas L. Petrakis
Department of Epidemiology and International Health
School of Medicine
University of California

Dr. R. Neil Schimke
Division of Metabolism, Endocrinology and Genetics
University of Kansas Medical Center

Dr. Arthur C. Upton
School of Basic Health Science
State University of New York Health Science Center

JAPAN
Dr. Kaoru Abe
Endocrinology Division
National Cancer Center Research Institute

Dr. Takashi Sugimura
National Cancer Center Research Institute

Dr. Satoshi Ebihara
Department of Head and Neck Surgery
National Cancer Center Hospital

Dr. Toru Ise
Department of Pediatrics
National Cancer Center Hospital

Dr. Fujio Kasumi
Department of Surgery
Cancer Institute Hospital

Dr. Yukio Shimosato
Pathology Division
National Cancer Center Research Institute

Dr. Keiichi Suemasu
National Cancer Center Hospital

Dr. Ryosuke Tsuchiya
Department of Surgery
National Cancer Center Hospital

Dr. Kyosuke Ushio
Department of Diagnostic Radiology
National Cancer Center Hospital

Dr. Shaw Watanabe
Pathology Division
National Cancer Center Research Institute

Dr. Kazumasa Yamada
Department of Medicine
The Branch Hospital
Nagoya University School of Medicine


(2) SEMINAR ON NEW ETIOLOGY OF LUNG CANCER
Honolulu, Hawaii, March 21-23, 1983

AGENDA

PARTICIPANTS

UNITED STATES
Dr. Richard H. Adamson
Director, Division of Cancer Cause and Prevention
National Cancer Institute

Dr. Frederick A. Beland
Director, Carcinogenesis Research
National Center for Toxicological Research

Dr. Ian T.T. Higgins
Professor
Department of Pathology
School of Public Health
University of Michigan

Dr. Dietrick Hoffmann
Associate Director
Naylor Dana Institute for Disease Prevention
American Health Foundation

Dr. Charles M. King
Chairperson, Department of Chemical Carcinogenesis
Michigan Cancer Foundation
Meyer L. Pentis Cancer Center

Dr. Joellen Lewtas
Genetic Bioassay Branch
Toxicology Division
Health Effects Research Laboratory

Dr. Roger O. McClellan
Director, Lovelace Biomedical and Environmental Research Institute, Inc.
Inhalation Toxicology Research Institute

Dr. Thomas C. Pederson
Senior Research Scientist
Biomedical Science Department
General Motors Research Laboratories

Dr. Herbert S. Rosenkranz
Professor and Director
Center for the Environmental Health Sciences
School of Medicine
Case Western Reserve University

Dr. Dennis Schuetzle
Staff Scientist
Ford Motor Company
Science Research Laboratory

Dr. Jaroslav J. Vostal
Biomedical Science Department
American Health Foundation

Dr. Ernest Wynder
President
American Health Foundation

JAPAN
Dr. Takeshi Hirayama
Epidemiology Division
National Cancer Center Research Institute

Dr. Hitoshi Kasuga
Department of Public Health
School of Medicine
Tokai University

Dr. Hidetsuru Matsushita
Environmental Health
National Institute of Public Health

Dr. Masaaki Terada
Carcinogenesis Control Section
National Cancer Center Research Institute

Dr. Hiroshi Tokiwa
Department of Health
Environmental Pollution Study Center

Dr. Suketami Tominaga
Epidemiology Division
Aichi Cancer Center Research Institute

Dr. Yoshinari Onishi
Bacteriology, Faculty of Medicine
Tokushima University


(3) SEMINAR ON CARCINOGENESIS AND ENVIRONMENTAL FACTORS
Dedham, Massachusetts, March 28-29, 1983

AGENDA

PARTICIPANTS

UNITED STATES
Dr. Herman Autrup
Laboratory of Human Carcinogenesis
National Cancer Institute

Dr. F. S. Chu
Department of Food Microbiology and Toxicology
University of Wisconsin

Dr. John Essigmann
Laboratory of Toxicology
Department of Nutrition and Food Science
Massachusetts Institute of Technology

Dr. Michael A. Marletta
Toxicology and Food Chemistry
Department of Nutrition and Food Chemistry
Massachusetts Institute of Technology

Dr. Marsha Rosner
Assistant Professor of Toxicology
Department of Nutrition and Food Science
Massachusetts Institute of Technology

Dr. Stephen Hecht
Division of Environmental Carcinogenesis
Naylor Dana Institute of Disease Prevention

Dr. Ronald Hites
School of Public and Environmental Affairs and Department of Chemistry
Indiana University

Dr. Fred Kadlubar
Chemistry Division
National Cancer Center for Toxicology Research

Dr. Steven R. Tannenbaum
Professor of Toxicology and Food Chemistry
Department of Nutrition and Food Science
Massachusetts Institute of Technology

Dr. William Thilly
Genetic Toxicology
Department of Nutrition and Food Science
Massachusetts Institute of Technology

JAPAN
Dr. Yuzo Hayashi
Chief, Division of Pathology
National Institute of Hygienic Sciences

Dr. Hikoya Hayatsu
Professor of Bio-organic Chemistry
Faculty of Pharmaceutical Sciences
Okayama University

Dr. Tadao Kakizoe
Department of Urology
National Cancer Center Hospital

Dr. Taijiro Matsushima
Professor of Molecular Oncology
Institute of Medical Science
Tokyo University

Dr. Minako Nagao
Head, Biochemistry Division
National Cancer Center Research Institute

Dr. Hirohisa Omura
Professor of Food Science and Technology
Faculty of Agriculture
Kyushu University

Dr. Shigeaki Sato
Chief, Biochemistry Division
National Cancer Center Research Institute

Dr. Shozo Takayama
Vice Director
Cancer Institute, Japanese Foundation for Cancer Research