SUMMARY OF ACTIVITIES

The year April 1, 1979 to March 31, 1980 constitutes the first year of the second Five-Year Program of the U.S.-Japan Cooperative Cancer Research Program. The major objective of the Etiology Area of this Program is to identify carcinogenic factors and clarify mechanisms of carcinogenesis with a view to providing a fundamental basis for understanding the causation of human cancer.
The etiology area includes four sub-areas, namely; Epidemiology, Chemical Carcinogenesis, Viral Carcinogenesis and Genetics. These four areas are closely inter-related and the seminars held during the past year reflect this fact. For example, the seminar entitled “Gastrointestinal Tract Cancer” held in Honolulu in March, 1980 brought together scientists from different disciplines, including epidemiology, pathology, and biochemistry. The discussions focused in two major gastrointestinal cancers-colon and stomach, which are prevalent in the U.S. and Japan, respectively. These geographic differences in incidence provided a useful contrast for discussions on etiology, the possible roles of initiators and promoters, precancerous lesions, and preventive studies.
Progress in our understanding of the etiology of cancer is closely coupled to our understanding of the normal mechanisms that control cellular growth and differentiation. For this reason, a seminar titled “Molecular Mechanisms of DNA Synthesis in Cancer Cells” was held in March, 1980 in Tokyo. This conference provided an extremely fruitful exchange of information between U.S. and Japanese scientists of new information in this important and rapidly moving field of basic research.
More detailed reports of these two conferences are given in pp. 5-8.
Detailed reports of the progress submitted by the eleven individual Scientist Exchanges are given in pp. 18-29. All of these were highly successful. As examples, brief descriptions of two Scientist Exchanges are given in this section. The visit of Dr. N. E. Spingarn to the laboratory of Dr. T. Matsushima, University of Tokyo, was extremely effective. It resulted in rapid progress in identifying new mutagens found in broiled fish and fried hamburger. The complete chemical structures of these compounds is currently being elucidated and the results will soon be available. The results of these studies will be published as a collaborative effort from the National Cancer Center Research Institute in Japan and the American Health Foundation.
The visit of Dr. Kazuo Umezawa to Columbia University led to rapid progress in at least three areas related to the molecular mechanism of action of tumor promoters, especially at the level of cellular membranes. It was found that Staphylococcal delta hemolysin, an amphipathic polypeptide, inhibits the binding to cellular receptors of epidermal growth factor (EGF); this compound also exerted other effects on cell membranes similar to the phorbol ester tumor promoters.
In a second set of studies, evidence was obtained that the specificity of cell receptor responses to a series of phorbol ester compounds is different in rodent cells than in human cells. Dr. Umezawa's visit also stimulated a collaborative study among Drs. Umezawa, I. B. Weinstein and T. Sugimura on the membrane effects of teleocidin, a very potent and novel type of tumor promoter recently discovered in Japan. These collaborative studies are continuing and will shortly be submitted for publication. Although it has quite a different chemical structure, teleocidin is as active as the highly potent tumor promoter, 12-0-tetradecanoyl-phorbol-13 acetate (TPA). These collaborative studies indicate that teleocidin and TPA may act on the same cell surface receptors, despite the fact that these compounds have quite different chemical receptors.