Age-at-exposure dependence of radiation carcinogenesis in animal models of breast cancer

Abstract

Ionizing radiation is the only firmly established human breast carcinogen. Rodent mammary cancer is a useful model of human breast cancer and has been the central player in experimental breast cancer research. The dependence of cancer risk upon the age at carcinogenic exposure is an important issue.
Chemical carcinogenesis studies have clarified that there is a narrow window of susceptible period in the peripubertal stage, during which extensive mammary gland growth occurs. This window of susceptibility may be explained by either differentiation state of the mammary gland, maturation of the potential for metabolic activation of carcinogens, or transition of the DNA repair capacity.
We have examined the effect of the age at exposure on radiation carcinogenesis. In contrast to chemical carcinogenesis, the susceptibility is relatively low during the juvenile period. Our data indicate that, although the immature gland may be susceptible to carcinogens, juvenile radiation exposure leads to relatively low incidence of mammary cancer through premature ovarian dysfunction and subsequent insufficient tumor promotion, suppressing hormone-dependent cancer development. Molecular mechanisms of radiation-induced carcinogenesis will also be discussed.