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Abstract:
In the experiments with various carcinogenic agents (chemical, radiation, hormonal) it was established that in aging sensitivity of different tissues to initiating action of carcinogens changes unequally. It could be attributed both to peculiarities of an agent (of indirect or direct action and others) and to age-related changes in the activity of DNA-repair systems and proliferative activity of target tissues. It appeared that old age, as a rule, facilitated transplantability and growth rate of various grafted tumors. There has been suggested a model according to which age-related increase of tumor incidence results from total action on the organism of stochastic (independant of age, environmental carcinogenic factors) and non-stochastic internal factors, developing with age in the organism. Stochastic constituent is determined by the effective dose of a carcinogen and could be constant in any age. Accumulation of such a dose adds to the increase of cancer incidence with age. Nonstochastic constituent reflects the rate of age-related changes of the factors, determining the effective dose of a carcinogen and sensitivity of a target-tissue to its action (activity of carcinogen-metabolizing enzymes, DNA-repair, proliferative activity of the tissue in the moment of action) and factors of promotion and progression of carcinogenesis (immunity and hormono-metabolic status). The value of this parameter is different for every tissue. With regard to this model, organization of primary prevention of cancer should provide alongside with measures aimed at prevention of environmental carcinogenic action on the organism, those, inhibiting age-related shifts in the organism, which facilitate cancer development.