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Coordinators: |
Dr. Arthur C. Upton
Dr. Takashi Sugimura |
It has been estimated that eighty per cent of human cancer cases are caused by chemical carcinogens in the air and in the foods. Chemical carcinogenesis is one of the most important research subjects for the conquest of human cancer. Since this research area includes a wide range of further specialized subareas: chemistry of chemical carcinogens, metabolism of carcinogenic substances, mechanism of cancerization, correlation between carcinogenesis and cell membrane alteration, ontogeny and oncogeny, carcinogenesis and mutation, precancerous status, protection from cancerization, establishment of clinical models, detection of carcinogens in the environment, relation of chemical carcinogenesis to viral carcinogenesis, and so forth, all the activities in this area are to be negotiated between the coordinators not only on a narrow, specialized subject basis, but also on the timely and urgent subareas.
Duplication of the research subjects with the U.S.-Japan Medical Science Program, Environmental Mutagenesis and Carcinogenesis Panel, has been and will also be avoided in the future.
There have been antecedent efforts in research on chemical carcinogenesis in Japan and the United States and the cooperation in this special field of cancer research is considered extremely beneficial to both countries. The scientific seminars, exchange of scientists, and exchange of information resources and latest research techniques so far carried out under the program, have been helpful to the respective sides in establishing the research strategy and research systems.
One aspect to be emphasized in this program area is the search for possible application of protease inhibitors as protection from cancer. In the joint seminar entitled “Action of Protease Inhibitor and Carcinogenesis” held in March 1975 in Hawaii, the effects of protease inhibitors on carcinogenesis and metastasis were discussed. The conference talks led to the conclusion that proteases play an important role in carcinogenesis, although their mechanism remains to be disclosed. Possibilities include activation of inactive precursors of carcinogens, depression of the genome, and activation of hormones. Inhibition of proteases was considered to be an important tool and to offer some prospects for specific biological control of the neoplastic processes. Through this seminar, distribution to the U.S. scientists of the commercially unavailable protease inhibitors, including 800 gr. of Leupeptin, 500 gr. of Pepstatin, 800 gr. of Antipain, and 600 gr. of Gulcanolactum, was arranged by JSPS. A committee has been set up to receive and review requests from U.S. investigators interested in obtaining some of the inhibitors for research purposes.
This program area also planned a U.S.-Japan-Australia tripartite conference on “Modified Cellular and Molecular Controls in Neoplasias”, which was held in Hawaii in December 1975. This conference was sponsored by JSPS, NCI, the National Science Foundation U.S.A. and the Australian Department of Science. The theme of the conference was timely in view of recent advances in developmental biology, cell regulation, and somatic cell genetics. The conference focused on the four aspects of cellular control: 1) action of steroid hormones, 2) action of polypeptide hormones (cyclic nucleotides), 3) transcriptional controls, and 4) post-transcriptional controls, topics which are particularly active and promising lines of research at the present time. Hence, this type of conference was helpful to cancer investigators in relating newer developments in these fields to the study of neoplasia. In this seminar, disorders of metabolic control and abnormality in differentiation were emphasized as phenotypic changes in cancerization. Relevancy of the study on hormone receptors and cyclic nucleotides may exist both in clarifying a neoplastic status and in offering a system in which functions of those hormone receptors and cyclic nucleotides are investigated.
In order to explore approaches for improving the methodology of carcinogenicity testing in animals, a scientific seminar on “Evaluation of Methods of Carcinogenesis in Mammals” was held in Japan in November 1975, at which time the development and standardization of criteria and protocols for carcinogenecity testing were discussed. Since the U.S. and Japan are both heavily involved in carcinogenicity testing, the sharing of experience and expertise in this field should be mutually beneficial in exploring available approaches, avoiding unnecessary duplications of effort, and enabling limited resources to go further toward meeting the existing and urgent needs.
The other aspect to be pointed out in this area exists in rapid screening of chemical carcinogens. Mutagenic potentiality of chemical carcinogens has been most efficiently applied. Japanese scientists were sent to the U.S. laboratories to discuss techniques in rapid screening of chemical carcinogens and also the data processing with computers. U.S. scientists were also sent to Japan for a thorough examination of mutagenicity of those commercially available hair dyes in Japan.