Abstract 5579: Selenomethionine does not protect against testosterone plus 17 beta-estradiol-induced prostate carcinogenesis and prostatic oxidative stress in NBL rats (original) (raw)

2011

Abstract

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Previous studies with selenium and/or vitamin E in prostate carcinogenesis animal models have been negative, but these models may not involve oxidative stress mechanisms. Selenium and vitamin E have been the subject of one of the largest trials ever conducted, SELECT, which was discontinued because there was no difference between the study arms and there were side effects, including an increased chance of developing diabetes mellitus with the use of selenium. We previously found that selenomethionine supplementation did not prevent prostate cancer in NBL rats treated with testosterone plus 17 beta-estradiol (T+E2), a model that does involve sex-hormone induced oxidative stress mechanisms and prostatic inflammation; this result was fully predictive of the outcome of the SELECT trial. Based on the outcomes of SELECT and our NBL rat study, we hypothesized that selenium has no protective effect against T+E2-induced prostate cancer development because it does not protect against oxidative stress. In the present study, we examined the potential of selenomethionine to modulate prostatic oxidative stress and induction of dysplasia and inflammation in the T+E2-treated NBL rat. Nbl/Crl rats were treated for 16 weeks with T+E2 by Silastic implants and were fed a natural ingredient control diet (NIH-07) with or with L-selenomethionine at a concentration of 1.5 or 3.0 mg/kg (as selenium). These diets were initiated one week post hormone implantation. T+E2 significantly increased immunohistochemical staining for 8-hydroxy-deoxyguanosine (8-OHdG) in prostatic ducts, and in the lateral and dorsal prostate which are the main sites of T+E2-induced inflammation and preneoplasia after 16 weeks of hormone treatment, and in the seminal vesicles. However, selenomethionine did not reduce these effects and did not, by itself, change 8OHdG staining. There was a lobe-specific differential response and modulation of antioxidant enzymes. Glutathione peroxidase activity and protein expression level of manganese superoxide dismutase were induced by T+E2, which effects were counteracted by selenomethionine in the dorsolateral prostate, which is the main site of T+E2-induced inflammation and preneoplasia occurring after 16 weeks of hormone treatment. However, selenomethionine did not influence the induction by T+E2 of marked inflammation and dysplasia in the lateral prostate. These findings partially explain the negative outcome of our previous NBL rat study and is consistent with the negative results of the SELECT trial. (Supported in part by Grant No. CA104334) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5579. doi:10.1158/1538-7445.AM2011-5579

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