DIVERSITY AND COMPLEXITY OF CARCINOGENIC PROCESSES - CONCEPTUAL INFERENCES FROM FOREIGN-BODY TUMORIGENESIS

A defect in the cellular growth control system appears central to every carcinogenic process. A comprehensive understanding of carcinogenic processes may remain out of reach as long as the mechanisms of normal cell regulation and growth control are not elucidated. Numerous groups of agents with diverse modes of action are known to cause cancer. The initial affection of the cell and also the cellular sites at which the primary events take place must be as varied. Yet the end result, cellular neoplastic autonomy, is obviously the same. Some segment of the developmental cell path toward neoplastic autonomy must be common to all forms of carcinogenesis. The extent of such carcinogenic uniformity is a matter of basic controversy. Certain virologic hypotheses imply that, by activation of a specific inherent oncogenic virus or genome, the carcinogenic process is a universal one at the primary event and thereafter. The observations of FB [foreign body] tumorigenesis in context with findings on other tumor induction models suggest that the only common event may be the terminal breakdown of the cellular growth control system. The collapse of this multifunctional composite could come about in different ways which may be targeted at 1 of various interlocking functional subunits after having been initiated by 1 of many possible key events. The model of FB tumorigenesis appears particularly suited for studying the multifactorial in vivo process of carcinogenesis. While the natural preneoplastic events and developments run their course in the animal, cell samples can be periodically taken for culture, cloning and expansion. Analytic results obtained on such cell preparations at different preneoplastic maturation stages can be related retrospectively, in the case of homology, to specific tumor characteristics.