title: Sex hormone-induced nuclear DNA damage and lipid peroxidation in the dorsolateral prostates of Noble rats.
abstract: 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.
authors.affiliation: Department of Biology, Tufts University, Medford, MA 02155.
authors.forename: S M
authors.initials: SM
authors.lastname: Ho
authors.forename: D
authors.initials: D
authors.lastname: Roy
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004249:DNA Damage; D004958:Estradiol / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008297:Male; D011467:Prostate; D051381:Rats; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D013739:Testosterone; D004958:Estradiol