L-selenomethionine does not protect against testosterone plus 17β-estradiol-induced oxidative stress and preneoplastic lesions in the prostate of NBL rats.
Previous animal studies examining dietary selenium effects on prostatic carcinogenesis did not show preventive benefit, including 1 study in a rat model involving testosterone (T) and estradiol (E2)-induced prostatic oxidative stress. Here, we examined modulation of T + E2-induced prostatic oxidative stress, dysplasia, and inflammation by L-selenomethionine at 1.5 or 3.0 mg selenium/kg in NIH-07 diet in Noble (Nbl)/Crl rats treated with T + E2 for 16 wk. Hormone treatment increased immunohistochemical staining for 8-hydroxydeoxyguanosine (8-OHdG) in the prostatic sites of T + E2-induced preneoplasia (P < 0.05), but selenomethionine did not attenuate 8-OHdG staining and dysplasia in the lateral prostate. Glutathione-peroxidase activity (P < 0.05) and mRNA expression were induced by T + E2 (P < 0.0001) but not changed by selenomethionine. Selenomethionine did not cause significant responses in expression and activity of glutathione-peroxidase and MnSOD, except for a reduction of MnSOD protein expression in the lateral prostate (P < 0.01). The absence of reduction of oxidative stress and dysplasia and the minimal effects on antioxidant enzymes caused by selenomethionine are consistent with the null effects observed in selenium supplementation animal studies and clinical trials. Significant (P < 0.01) opposite apoptosis/cell proliferation balance responses to selenomethionine and to T + E2 occurred in the lateral and dorsal prostate, explaining why T + E2 induces lesions selectively in the lateral lobe of NBL rats.
a University of Illinois at Chicago, School of Medicine , Department of Pathology , Chicago , Illinois , USA.
Nur
N
Özten
Michael
M
Schlicht
Alan M
AM
Diamond
Maarten C
MC
Bosland
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D019587:Dietary Supplements; D004958:Estradiol / Q000009:adverse effects*; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control*; D011467:Prostate / Q000187:drug effects* / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D012643:Selenium / Q000008:administration & dosage; D012645:Selenomethionine / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013739:Testosterone / Q000009:adverse effects*
D020011:Protective Agents; D013739:Testosterone; D004958:Estradiol; D000080242:8-Hydroxy-2'-Deoxyguanosine; D012645:Selenomethionine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003849:Deoxyguanosine; D012643:Selenium