Radiation exposure during the peri-pubertal period is a proven risk factor for
breast cancer, whereas parity is an established protective factor. The present study investigated whether parity imposes differential protective effects against radiation-induced rat mammary
carcinoma depending on the age at exposure. Pre- and post-pubertal female rats, irradiated or left unirradiated, were mated and allowed to nurse until weaning or left unmated. Appearance of mammary
tumors was monitored, and serum concentrations of
estradiol and
progesterone were measured following weaning.
Carcinomas were evaluated by immunohistochemistry for
estrogen receptor,
progesterone receptor, and the cell proliferation marker Ki-67. Parity reduced the risk of
carcinoma in unirradiated and pre-pubertally irradiated rats but not post-pubertally irradiated rats. Although radiation exposure increased serum
progesterone level, parity after pre-pubertal exposure significantly decreased the elevated
progesterone to a normal level, reflecting a protective effect. Moreover, parity significantly decreased the proportion of
hormone receptor-positive
carcinomas after pre-pubertal exposure. Parity was also related to the observed positive association between
progesterone receptor and Ki-67 indices in
cancer tissue, implying
progesterone receptor-dependent cell proliferation. Thus, parity protects against radiation-induced rat mammary
carcinogenesis depending on the age at exposure; the mechanisms may involve changes in
hormone levels and
cancer tissue.