Challenging problems in cocarcinogenesis.


The role of hormones as sensitizers in mammary carcinogenesis can be surmised on a priori grounds: (a) from general evidence of hormone involvement in the maturation of mammary tissue; (b) from differences in incidence of mammary tumors between the sexes; (c) from dietary influences on the incidence of mammary tumors, a high-fat diet affecting the hormonal status of the body (8); and (d) more specifically, from the role of hormones in the development of hypertrophie alveolar nodules, the precursors of mammary tumors in mice (48). The induction of mammary tumors by gastric instillation or injection of polycyclic aromatic hydrocarbons (35, 61) provided a reliable means of distinguishing between hormonal effects according to the times of administration, i.e., before, during, or after the carcinogenic action. We are concerned here only with the effects before the start of carcinogenic action. It was thus possible to show that neoplastia transformation of mammary tissue (the initiating phase of carcinogenesis in that organ) failed to take place in the rat in the absence of ovarian hormonal participation (15). [Dependence on hormonal stimula tion had been demonstrated previously under different condi tions, specifically, in male mice receiving ovarian grafts prior to chemical carcinogenic action (42).] Mammary carcinogenesis is the result of a complex series of events, with different hormones operating during the various stages of maturation of the organ. Consequently, apart from involvement in the carcinogenic process (23, 36) and the partic ipation of a virus, at least in some strains of mice, convincing demonstration of hormonal preparative action, as distinct from permissive (see later section) or promoting action, is not as clearcut or straightforward a process in mammary carcinogenesis as is the case of many other tissues or organs. In an earlier analysis of modifying influences in chemical car cinogenesis (3), I defined the different forms of cocarcinogenesis as follows: (a) additive action by a modifying agent that itself possesses carcinogenic activity; (b) syngeneic action (in the pharmacological sense) in which the combined action of the 2 agents exceeds the summation of their separate effects; (c) incomplete carcinogenic action by a modifier responsible for only one of the phases of carcinogenesis, i.e., either initiation or promotion; (d) preparative action, rendering the target tissue more responsive to the action of the inciting agent; (e) permissive influence on the action of the carcinogen itself through solvent effects, metabolism, etc.; (f) effects on the action of a virus, e.g., activation of a latent virus or depression of the host's immune


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@article{Berenblum1985ChallengingPI, title={Challenging problems in cocarcinogenesis.}, author={Isaac Berenblum}, journal={Cancer research}, year={1985}, volume={45 5}, pages={1917-21} }