title: Protective effect of zinc on N-methyl-N-nitrosourea and testosterone-induced prostatic intraepithelial neoplasia in the dorsolateral prostate of Sprague Dawley rats.
abstract: Previous studies have suggested that zinc exerts anticarcinogenic and antiproliferative effects against prostate cancer both in vitro and in rat ventral prostate. Zinc accumulation diminishes early in the course of prostate malignancy and it inhibits the growth of several carcinoma cells through induction of cell cycle arrest and apoptosis. In this study, we have investigated the influence of zinc on N-methyl-N-nitrosourea (MNU) and testosterone (T)-induced prostatic intraepithelial neoplasia in the dorsolateral prostate of Sprague Dawley (SD) rats. The results indicate that zinc plays an important role in prostate carcinogenesis. Increased tumor incidence was accompanied by a decrease in prostatic acid phosphatase activity, citrate, zinc, glutathione-S-transferase, reduced glutathione, p53, B-cell lymphoma protein (Bcl-2)-associated X protein and caspase-3 levels in MNU + T-treated rats. On the contrary, significantly increased phase I drug metabolizing enzyme activities, lipid peroxide, hydrogen peroxide, proliferating cell nuclear antigen, Bcl-2 and Bcl-X(L) protein levels were observed in the dorsolateral prostate of MNU + T-treated rats. Simultaneous zinc supplementation significantly reversed these effects in MNU + T-treated rats. Signs of dysplasia, a characteristic of prostatic intraepithelial neoplasia, were evident in the dorsolateral prostatic tissue sections by MNU + T administration. However, zinc supplementation has reversed these effects in the dorsolateral prostatic histoarchitecture. These results suggest that zinc may act as an essential trace element against MNU and testosterone-induced prostatic preneoplastic progression in SD rats.
authors.affiliation: Department of Endocrinology, Dr ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, Tamilnadu, India.
authors.forename: Sivanantham
authors.initials: S
authors.lastname: Banudevi
authors.forename: Perumal
authors.initials: P
authors.lastname: Elumalai
authors.forename: Govindaraj
authors.initials: G
authors.lastname: Sharmila
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Arunkumar
authors.forename: Kalimuthu
authors.initials: K
authors.lastname: Senthilkumar
authors.forename: Jagadeesan
authors.initials: J
authors.lastname: Arunakaran
mesh_terms: D000135:Acid Phosphatase; D000818:Animals; D015153:Blotting, Western; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D008770:Methylnitrosourea / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D011471:Prostatic Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D017967:Zinc Compounds / Q000494:pharmacology*
chemical_list: D002273:Carcinogens; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D017967:Zinc Compounds; D013739:Testosterone; D008770:Methylnitrosourea; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases