Role of age in host sensitivity to carcinogens.

The possible mechanisms of age-associated changes in host sensitivity to carcinogenic agents are discussed. It has been suggested that the main modifying factors of carcinogenesis in aged organisms are age-associated shifts in: (1) activity of carcinogen-metabolizing enzymes in liver and other target tissues; (2) binding of active carcinogen metabolites to macromolecules (nucleic acids and proteins); (3) accuracy of DNA repair; and (4) proliferative activity of target tissue, regulated by tissue-specific factors (chalones and growth factors), hormones and some metabolic factors (cholesterol, fatty acids). A scheme of carcinogenesis is presented which integrates the effects of carcinogens at subcellular, tissue and organism levels.