Exogenous 17 beta-estradiol blocks alpha and mu but not pi class glutathione S-transferase immunoreactivity in epithelium of Syrian hamster vas deferens

Members of the glutathione S-transferase (GST) family of detoxification enz ymes play a role in chemotherapy resistance in certain cancers but have not been directly implicated as agents whose absence may predispose tissues to hormonally induced tumorigenesis. Here we report the development of a poly clonal antiserum to a hamster mu class CST, and immunohistochemical analysi s of alpha, mu, and pi class GSTs to study the effects of hormone treatment on their expression in reproductive tract tissues of male golden Syrian ha msters. These animals develop leiomyosarcomas in the vas deferens after tre atment with testosterone propionate (TP) and 17 beta-estradioil (E2). High levels of all three GST classes were detected throughout the reproductive t ract epithelium of control animals. In 100% of the experimental animals, 4 weeks of treatment either with E2 alone, or with E2 plus TP promoted a comp lete loss of immunostaining for alpha and mu class GSTs, but not for pi cla ss GSTs, only in the epithelial lining of the vas deferens. In contrast, tr eatment with TP alone resulted in moderate hyperplasia of smooth muscle in the proximal vas deferens, with no cellular atypia and no changes in immuno reactivity of any of the GST classes. The consistent and site-specific natu re of these results strongly suggests a functional role for GSTs in hormona lly induced carcinogenic process.