New principle for the analysis of chemical carcinogenesis

THE development of cancer following exposure to chemical carcinogens or to various forms of irradiation is almost invariably slow and prolonged. Although the process can be initiated by a brief exposure to a carcinogenic stimulus, there is no evidence that target cells so altered are cancer cells. Rather, there is abundant indirect evidence from many systems that what is induced is an altered cell or cell population from which malignant neoplasia can gradually develop or evolve^1,2. Neoplastic development therefore resembles a chain reaction, triggered by exposure to a carcinogen, in which the links are new populations with altered organisational, structural and biochemical properties. These slowly proliferative new lesions are characteristically focal in distribution, implying that only a small proportion of the original target cell population in any organ or tissue participates. It is not known what the critical property (or properties) is that makes initiated cells so important in carcinogens and the failure to understand and manipulate this early step has been a major impediment to its analysis.