Abstract 1264: Studying senescence in prostate of selenium treated rats undergoing carcinogen-induced, androgen-promoted prostate carcinogenesis
Authors: Kartick C. Pramanik, Michael Schlicht, Maarten Bosland, Chang Jiang, Yibin Deng, Junxuan Lu
Journal: Cancer Research (2017)

Abstract Preclinical studies from us and others have shown that oral intake of next-generation selenium (Se) forms, especially methylseleninic acid (MSeA) and Se-methylselenocysteine (MSeC) inhibits mouse prostate carcinogenesis. Our recent study has shown that MSeA suppresses pten-deficient mouse high grade prostatic intraepithelial neoplasia progression to adenocarcinoma in association with superactivating p53-p21 mediated cellular senescence. To address the question whether the activation of senescence is induced in prostate carcinogenesis driven by different etiology, we sought to test the in vivo effect of different selenium forms fed to rats undergoing chemically induced, androgen promoted prostate carcinogenesis. Wistar-Unilever (WU) rats (10-12 wks) were sequentially treated with androgen receptor blocker flutamide for 21 days (10 mg/kg/day by gavage), followed by testosterone propionate (TP, 10 mg/kg, s.c) on day 22. Three days after TP, chemical carcinogen methylnitrosourea (MNU, 30 mg/kg/bw) was administered by i.p. injection. One week later, the rats received testosterone-containing silastic implants. Rats were randomized to groups fed the AIN-93M diet or supplemented with 3 ppm of Se as MSeA, MSeC, or selenomethionine (SeMet). Separate groups of rats were fed these diets, but did not receive the carcinogen treatment. After 16 weeks of this dietary treatment, rats were euthanized. Blood, major organs and different prostate lobes were dissected and weighed. The body weight of carcinogen-exposed rats was significantly lower than their non-carcinogen-exposed counterparts. However, total prostate complex weight was higher in carcinogen-treated groups than the non-carcinogen groups, consistent with MNU and extra-testicular androgen promoting prostate epithelial cell proliferation. There were no significant organ-to-body weight ratio differences of various prostate lobes in the different dietary groups, regardless of the carcinogen exposure status. In order to test the involvement of senescence in prostate of rats fed different Se diets, we have undertaken steps to optimize staining method for senescence-associated β-galactosidase (SA-βgal) activity in different lobes of prostate frozen sections. Together, with whole slide imaging using an Aperio Digital Pathology Scanner for quantitation, we are afforded an approach for more objective interrogation of the role of senescence in this carcinogenesis model and chemoprevention by selenium compounds. Citation Format: Kartick C. Pramanik, Michael Schlicht, Maarten Bosland, Chang Jiang, Yibin Deng, Junxuan Lu. Studying senescence in prostate of selenium treated rats undergoing carcinogen-induced, androgen-promoted prostate carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1264. doi:10.1158/1538-7445.AM2017-1264