The scientific basis for carcinogen detection and primary cancer prevention

The primary prevention of specific human cancers must take into account the likelihood that most cancers result from a complex interaction between multiple environmental (exogenous) and host (endogenous) factors. In addition, the carcinogenic process often proceeds via multiple steps, including initiation, promotion, and progression. Therefore, assays are required that detect not only initiating carcinogens, but also tumor promoters, hormones, and various cofactors. The known biologic and biochemical properties of initiating carcinogens are reviewed and contrasted with those of tumor promoters. The implications of these differences with respect to the detection and assay of these agents are stressed. At present, the assay for tumor induction in rodents represents the major laboratory approach to carcinogen detection. The advantages and limitations of such studies are discussed. Certain recently developed short-term tests for detecting initiating carcinogens are critically evaluated. Progress has also been made in the development of short-term assays for tumor promoters and in vitro systems that demonstrate synergistic interactions between initiating chemical carcinogens, promoters, and oncogenic viruses. Problems encountered in extrapolating findings from rodent bioassays and from short-term tests to the assessment of human risks are emphasized. Much more emphasis must be given to studies that integrate human clinical, laboratory and epidemiologic approaches, if we are to achieve more rational approaches to cancer prevention.