Estrous cycle modulation of O6-alkylguanine-DNA alkyltransferase expression in rat mammary epithelial cells.

Abstract

N-methyl-N-nitrosourea (MNU)-induced rat mammary tumor incidence and tumor number per rat, is directly correlated with an increase in the circulating level of estrogen(s) at the time of carcinogen administration and subsequent mammary epithelial O6-methylguanine content. We report that, expression of O6-alkyltransferase (AGT) is also regulated by reproductive hormones in a tissue specific manner. The level of mammary epithelial cell AGT activity on estrus (0.47 pmol/mg protein) and proestrus (0.32) was significantly higher than on metestrus (0.14) (P < 0.05, estrus vs. metestrus). However, no change was observed in liver AGT activity (0.52 pmol/mg protein). In contrast, the mean level of AGT protein was not significantly different between tumors from rats injected with MNU on different days of the estrous cycle. In conclusion, the different tumor biologies resulting from carcinogen injection on different days of the estrous cycle may be partially explained by variation in levels of DNA repair activity. However, the cells in the resulting tumors did not continue an obligatory differential expression of the AGT activity consistent with their stage of initiation.