J Cancer Res Clin Oncol (2011) 137:677–686 DOI 10.1007/s00432-010-0926-4 123 ORIGINAL PAPER Chemopreventive eVects of zinc on prostate carcinogenesis induced by N-methyl-N-nitrosourea and testosterone in adult male Sprague-Dawley rats S. Banudevi · P. Elumalai · R. Arunkumar · K. Senthilkumar · D. N. Gunadharini · G. Sharmila · J. Arunakaran Received: 5 April 2010 / Accepted: 26 May 2010 / Published online: 16 June 2010  Springer-Verlag 2010 Abstract Purpose Zinc is an important micronutrient involved in structural and regulatory functions in mammalian cells. It inhibits proliferation of both androgen-dependent and -independent prostate cancer in vitro. However, no report is available on the chemopreventive role of zinc on prostate cancer initiation in in vivo model. The main purpose of this study was to assess the chemopreventive eVects of zinc on prostate carcinogenesis induced by a single dose of N-methyl-N-nitrosourea (MNU) and continuous testosterone administration in Sprague-Dawley rats. Methods In this study, prostate cancer was induced in Sprague-Dawley rats using MNU+ testosterone (MNU + T). Rats were simultaneously treated with zinc (100 ppm) thrice a week. Serum and tissue activity of prostatic acid phospha- tase (PAcP) was measured using biochemical analysis. Serum and tissue zinc levels were assessed by atomic absorp- tion spectrophotometry. The ventral prostatic citrate level, phase I drug-metabolizing enzymes such as cytochrome P450, cytochrome b 5 , cytochrome b 5 reductase, cytochrome C reductase, phase II enzyme like glutathione-S-transferase, lipid peroxidation, hydrogen peroxide (H 2 O 2 ), and reduced glutathione were also analyzed by biochemical assays. Protein expressions of p53, proliferating cell nuclear antigen (PCNA), caspase-3, and B-cell lymphoma protein-X L (Bcl-X L ) were detected by Western blot analysis. Histopathological evaluation of ventral prostate was studied using hematoxylin and eosin staining method. Results MNU + T-treated rats showed 60, 50, and 30% of hyperplastic, dysplastic, and prostatic intraepithelial neoplas- tic changes, respectively, in ventral prostate, whereas MNU + T along with zinc-treated rats showed an incidence of each 10% of hyperplasia, dysplasia, and prostatic intraepi- thelial neoplasia in the ventral prostate. Serum zinc level and PAcP activity were signiWcantly increased in MNU + T-treated rats, whereas these were decreased in zinc-treated rats. The ventral prostatic PAcP and glutathione-S-transfer- ase activities, zinc, citrate, reduced glutathione levels, and protein levels of p53, caspase-3 were signiWcantly decreased in MNU + T-treated rats, whereas increased in zinc-treated rats. Phase I drug-metabolizing enzyme activities, lipid per- oxidation, H 2 O 2 levels, PCNA, and Bcl-X L levels were increased in MNU + T-treated rats, whereas these levels were restored to within normal limits in zinc-treated rats. Conclusion This study suggests that zinc may have a beneWcial eVect against MNU and testosterone-induced prostate carcinogenesis. Thus, it may act as a potential che- mopreventive agent in targeting the prostate cancer. Keywords Apoptosis · Chemoprevention · MNU · Prostate cancer · Prostatic intraepithelial neoplasia · Zinc Introduction Prostate cancer is a major public health concern worldwide since it represents one in 10 cases of cancer in men and is of the highest incidence than any other cancers (Jemal et al. 2008). It has been suggested that a change in the testoster- one level with advance in age is an important factor in initi- ation of benign prostatic hyperplasia and prostate S. Banudevi · P. Elumalai · R. Arunkumar · K. Senthilkumar · D. N. Gunadharini · G. Sharmila · J. Arunakaran (&) Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai, Tamilnadu 600113, India e-mail: j_arunakaran@hotmail.com; j.arunakaran@gmail.com