Sex hormone-induced nuclear DNA damage and lipid peroxidation in the dorsolateral prostates of Noble rats.

To date, few studies have been reported on any aspect of DNA damage in organs of intact animals. We and others demonstrated induction of high incidences of dysplasia, a precancerous proliferative lesion, and adenocarcinoma selectively in the dorsolateral prostates (DLPs) of Noble rats exposed to a long-term combined testosterone and estradiol-17 beta treatment (T + E2-treatment). We here report induction of a significant increase in DNA strand breakage and accumulation of lipid peroxidation fluorescent products in the DLPs, but not in the ventral prostates (VPs), of rats treated with T + E2 for 16 weeks. These results indicate that this dual hormone treatment has free radical-based DNA damaging effect on rat DLP and therefore may have tumor-initiating action. Since a similar effect was not observed in regenerating DLPs of castrated rats following testosterone replacement, we conclude that the genotoxic effect of the dual hormone treatment is a direct result of hormone action and not secondarily due to enhancement of cell proliferation.