Quantitative and immunohistochemical evaluation of PCNA, androgen receptors, apoptosis, and Glutathione-S-Transferase P1 on preneoplastic changes induced by cadmium and zinc chloride in the rat ventral prostate

BACKGROUND. This study was directed to evaluate the immunoexpression of markers for cell proliferation, apoptosis, nuclear androgen receptors, and Glutathione-S-Transferase P1 (GSTP1), in preneoplastic changes induced by cadmium chloride (Cd) and cadmium plus zinc chloride (Cd + Zn) in rat prostate. METHODS. The following parameters were calculated in ventral prostate of normal rats and rats that received Cd or Cd+Zn in drinking water during 24 months: numerical densities of columnar, basal, and GSTP1 immunoreactive epithelial cells; percentages of cells immunoreactive to: PCNA, (LI(PCNA)), androgen receptors (LIAR), and of apoptotic cells. RESULTS. The LI(PCNA) was significantly increased in the animals exposed to Cd + Zn, whereas the numerical densities of both columnar (N, columnar cells), and GSTP1 immunoreactive (N(v)GSTP1+) cells were significantly increased in the animals treated with metals in comparison with the controls. No significant differences between the two sources of dysplasias (Cd and Cd+Zn) respecting to LI(PCNA), N(v) columnar cells, and N(v) GSTP1+ were observed. The two types of dysplasias considered together showed a significant increase for the Nv basal, N(v) columnar, and N(v)GSTP1+ cells in comparison with normal acini of treated and controls. The percentage of apoptotic nuclei did not show significant differences among the three groups studied. CONCLUSIONS. (1) The zinc has little influence in the development of the dysplastic changes of the rat prostate mediated by cadmium. (2) The decrease of apoptosis has little influence in the development of dysplasia. (3) GSTP1 could play a role in the response to the oxidative stress in the dysplastic changes caused by cadmium. (c) 2004 Wiley-Liss, Inc.