PARENT SESSION
Prostate

CELL PROLIFERATION, APOPTOSIS, AND ANDROGEN RECEPTOR STATUS IN DYSPLASTIC LESIONS INDUCED BY CHRONIC EXPOSURE TO CADMIUM CHLORIDE IN RAT PROSTATE.

Santamaria, Luis¹, Martin, Rocio², Martin, Jose³, Pozuelo, Jose ⁴, Arriazu, Riansares⁴, Rodriguez, Rosario⁴, Henriques-Gil, Nuno⁵, ^{1 2 3 4 5}

ABSTRACT- The present study is addressed to characterize the androgen receptor status, cell proliferation, and apoptosis in epithelial dysplastic changes occurred in the prostate ventral lobe of rats treated by cadmium. We report the immunostainings to nuclear androgen receptor (AR) antibody and proliferating cell nuclear antigen (PCNA). Apoptosis was detected by TUNEL method. The study was carried out in 25 Sprague-Dawley rats without treatment by cadmium and in other 25 animals exposed to cadmium chloride (60ppm continually administered in drinking water during 24 months). Both control and experimental rats were killed at the end of experiment. The PCNA immunostaining, rate of apoptosis, and immunostaining for AR were evaluated by their respective labeling indices -LI_pcna, LI_apopt, LI_AR- (percentage of immunoreactive nuclei over the total of epithelial nuclei). The means +/- SD of all measurements were compared by ANOVA, in controls, experimentals, and dysplastic lesions. Multifocal dysplastic lesions in the acini of ventral lobe were observed in 5 rats. LI_pcna showed a significant increase (p<0.05) in dysplastic changes compared with controls and experimental (non dysplastic) glands. LI_apopt was significantly increased (p<0.05) in experimental (non dysplastic) acini in comparison with controls. However the LI_apopt of dysplatic cells was decreased to a similar level that observed in controls. The LI_AR was similar in both control and experimental (non dysplastic) acini. The chronic exposure to low concentrations of cadmium chloride causes epithelial dysplastic changes in ventral prostate, characterized by the increase of cell proliferation together with decreased expression of AR. The apoptosis experiments a transient rising in rats exposed to cadmium, nevertheless, it decreases in the dysplastic acini, this might correlate with the preneoplastic character of these lesions. These findings are similar to those described in the human prostatic intraepithelial neoplasia (PIN).

KEY WORDS: prostate dysplasia in rats, cell proliferation, apoptosis, androgen receptors