Efect Of Aging On The Susceptibility To Carcinogenesis In Vivo

Animal experiments seem to confirm that there are age related differences in sensitivity to carcinogen in some tissues. Thus, with age, susceptibility to carcinogens in murine mammary gland, small intestine and colon, thyroid, ovarian follicular epithelium decreases, in subcutaneous tissue, cervix uteri and vagina increases and in others (lung, hemopoietic tissues) it remains stable (Table 1). For details see references 1,5-6). Age-related differences in cancer susceptibility have been observed after exposure to the same carcinogens in experimental systems. For example, in female rats exposed to N-nitrosomethylurea (NMU) in doses 10, 20 or 50 mg/kg at the age of 3 month developed mammary carcinomas, tumors of the kidney, ovaries and colon. In contrast to young animals, the rats exposed to the same doses of the carcinogen at the age of 15 months showed a higher frequency of tumors of the corpus and cervix uteri, and a lower frequency of mammary and intestinal adenocarcinomas and tumors of the ovary and kidney 25. Comparison of the results with the data on DNA alkylation, synthesis and O6-methylguanine repair obtained on the same model suggests a critical role of age-related proliferative activity changes occurring in the target tissues in the mechanism of age in modifying the effect on carcinogenesis. Obviously, there are no common patterns of age related changes in DNA synthesis and repair or in proliferative activity of different tissues with age 15,6.

There are several possible reasons for this wide variation in experimental results. These include factors related to the experimental model and factors related to the tumor-host. Model-related factors involve the characteristics of different carcinogens (direct or indirect action, chemical structure, mechanism of action), route of administration, exposure duration, presence of local and systemic activity, and time of observation. Host-related factors involve animal species, strain, sex, and age. The effective dose of an indirect carcinogen, requiring metabolic activation, may vary significantly in old and young animals, because the activity of the enzymes necessary for carcinogen activation in the liver and/or target tissue(s) may change with age 5,2,27. Critical factors that determine the susceptibility of a tissue to carcinogenesis include DNA synthesis and proliferative activity of that tissue at the time of carcinogen exposure, and the efficacy of repair of damaged DNA. The

Table 1. Effect of aging on the susceptibility of laboratory rodents to carcinogenesis

(Anisimov, 1987; 1998)

Table 1. Effect of aging on the susceptibility of laboratory rodents to carcinogenesis

(Anisimov, 1987; 1998)

Target tissue

Carcinogenic agent

Effect of aging

Skin

DMBA, MCA, BP. TC, UV, [i-irradiation

t

Fast neutrons, electrone-irradiation

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