Cadmium and Zinc Chloride-induced Preneoplastic Changes in the Rat Ventral Prostate: An Immunohistochemical and Molecular Study

Cadmium chloride (Cd) is a toxicant that has been implicated in human prostate cancer (PCA). The goal of the present study was to evaluate the immunoexpression of markers for cell proliferation, apoptosis, resistance to apoptosis, and to determine mutations on segments of the bcl-2 gene, in preneoplastic lesions induced in rat prostate after treatment with Cd alone or in combination with zinc chloride (Zn). We evaluated: 1) The % of cells positively immunostained for the proliferating cell nuclear antigen (PCNA), 2) The % of apoptotic cells (evaluated by TUNEL), 3) The volume fraction of Bcl-2 immunostaining. 4) The mutations on a segment of 253 pb of bcl-2, in the ventral prostate lobe of normal and treated rats with Cd alone or in the presence of Zn in the drinking water for 18 mo. Our results indicate that the % of PCNA positive nuclei was significantly increased in preneoplastic prostatic acini of Cd-treated rats alone and in combination with Zn, compared to the normal acini of untreated animals. No significant changes were detected on the apoptotic rate or the volume fraction of Bcl-2. Moreover, no significant changes in the band pattern of the amplified segment of bcl-2 gene were observed after Cd treatment. In summary, our data indicate that, prostate dysplasia induced in rats by Cd increases proliferative activity, without significant changes in either apoptosis or bcl-2 immunoreactivity.