ETIOLOGY PROGRAM AREA

SUMMARY OF ACTIVITIES

The year April 1, 1986 to March 31, 1987 is the third year of the third five-year program of the U.S.-Japan Cooperative Cancer Research Program. The aim of the Etiology Program Area is to clarify the causes of human cancers and to determine the mechanisms of carcinogenesis. It has been envisaged that cancer prevention may be achieved eventually through progress in the science of cancer etiology.
Three seminars were held during this period, one in Japan and two in the United States The first seminar, “Marine Natural Products and Cancer Chemoprevention,” focused on the biology, chemistry and pharmacology of tumor promoters and inhibitors of tumor promotion from natural sources, in particular from field-collected marine organisms and cultural microalgae. Sceptrin, manoalide and sarcophytol A were the most interesting anti-tumor promoters presented. This seminar gave an indication to scientists of both countries of the significance and relevance of compounds obtained from field-collected marine organisms and cultural microalgae to the study of cancer chemoprevention.
The second seminar, “Trans-acting Factors in Viral Carcinogenesis,” focused on the molecular mechanisms of gene transactivation and the possible roles of these functions in oncogenesis. Functions of transacting factors encoded by human and other cancer viruses, such as SV40 or adenovirus, on the expression of these viral genes and on their effects on the expression of the host genes, were presented and discussed. There were also presentations of the possible functions of myb and myc gene products. Although the molecular mechanisms of these factors which involve in trans-activation remain to be clarified, participants were made aware, through this seminar, that these factors modulate host factor(s), directly or indirectly, to activate or repress the expression of either viral or host genes.
The third seminar, “Risk Assessment of Environmental Carcinogenic Factors,” included discussions on the components of risk assessment, hazard evaluation based on animal experimental data, the contribution of exposure level to risk assessment and the contributions of epidemiology and mathematical modeling to risk assessment. In the evaluation of risks from chemical carcinogens, the importance of biologically effective doses for various tissues was emphasized. In this context, an assay of the chemicals bound to DNA or of the proteins in human material was shown to be helpful. The degree to which lifestyle contributes to human cancer development and the proportion of human cancers which practically might be prevented were introduced, based on new calculations. Although the risk assessment of human cancer occurrence is still in an evolutionary state, much information was obtained which should prove helpful toward making risk assessment a more exact science.
Three scientists from Japan came to the United States as exchange scientists, conducting collaborative research in the areas of chemical carcinogenesis molecular biology and cancer biochemistry.
During this reporting period, 2.75 gm of 2-amino-8,8-dimethylimidazo-(4,5-f)quinoxaline (MEIQx) and 1.75 gm of 2-amino-3,4,8-trimethylimidazo-(4,5-f)quinoxaline (4,8 IQx) were shipped from Japan to the United States.