Risk assessment for possible carcinogens: a critical look

Our overall understanding of mechanisms of toxicology in relation to human disease, with prevention of disease as a major objective, depends in part on the development of an adequate number of ways to assess risks, both short term and long term. Despite the cost, the long duration of the test, and some pitfalls, the long-term animal tests remain, to date, the only reliable assay for possible carcinogens. Recent work has concentrated increasingly on the development of short-term tests to replace the long-term tests. Such a development would be most welcome from several points of view. To date, a variety of approaches have been or are being used. These include (1) activation to an alkylating agent with DNA as the most important target, generating possible mutations in DNA and DNA damage with or without repair, (2) induction of cell proliferation, at least a few cycles, with DNA synthesis as the major target, again favoring mutations, and (3) decrease in cell-to-cell communication (gap-junctional intercellular communication) as a supposed test for promotion. None of these proposed assays are reliable indices for possible carcinogenic effects of chemicals or other agents; the scientific basis for this negative conclusion is discussed.