Carcinogenesis and aging. III. The role of age in initiation and promotion of carcinogenesis.

The problem of an interrelation between carcinogenesis and aging is discussed from the point of view of the two-stage model of carcinogenesis. Data on the carcinogenic effect of subcutaneously administered benzo(a)pyrene (BP), intravaginally applied 7, 12-dimethylbenz(a)anthracene (DMBA), and intravenously injected N-nitrosomethylurea (NMU) to young and old animals are presented. Both the obtained results and data from available literature show the absence of a uniform effect of age on carcinogenesis. Age-associated dynamics of carcinogen-metabolizing enzyme activity, accuracy in DNA repair, and proliferative activity of target and non-target tissues have been discussed as the determinant factors for observed differences. Data on the growth rate of some transplantable tumors in young and old animals are also presented. As a rule, the above tumors grow more rapidly in old animals in comparison with young ones. The role of age-associated hormonal, metabolic, and immunological changes in tumor promotion is discussed. The similarity is stressed of a number of changes occurring at organism, tissue, and cellular levels of integration both during natural aging and carcinogenesis. Some results of study on effects of geroprotectors on spontaneous carcinogenesis are summarized. The geroprotectors, which were shown to delay the realization of the genetic programme of aging and age pathology development, prolong lifespan and inhibit carcinogenesis more effectively than those influencing the initiatial stage of spontaneous carcinogenesis. Finally, the integral scheme of events taking place in cell, tissue, and organism during carcinogenesis is presented.