The present study confirms previous reports regarding the role of Cd in rat prostate tumorigenesis (5). The changes observed resembling dysplasia have been previously described after Cd exposure and other carcinogenic agents (2,4). The lesions observed were histologically similar to those described as atypical hyperplasia induced in rats by treatment with phenylephrine (12). It should be noted that the changes from untreated acini to those of non-dysplastic and dysplastic acini from Cd-treated rats display a continuum (2). Cd intake may induce initial changes in the prostatic epithelium by increasing cell proliferation. This assumption agrees partially with other descriptions of Cd effects on rat male genital organs because, in contrast to other reports (2), we did not find an increase in apoptosis. Although, it has been reported that Zn may have a potentiating effect on prostatic tumorigenesis (13), in the present study, we did not observed neither an effect on cell proliferation or apoptosis after Zn exposure. Bcl-2 expression was increased in Cd ± Zn-exposed rats, in comparison to untreated animals; however these differences were not significant, contrary to previous studies (2). No differences in bcl-2 gene band pattern were observed in any of the groups examined indicating that the mutation rate for this gene was lower than expected. Differences in PCNA and Bcl-2 expression and localization between rat and human prostates were remarkable. In normal human prostate, the proliferation compartment is better defined than in rat prostate. It is represented by isolated cells and often is absent in some portions of the acini (the basal layer, PCNA and Bcl-2 positive). Moreover, proliferative activity in the rat is not confined to the basal cells. It has been reported that the main proliferating cells in rat prostate are the columnar cells (14). Cd-induced prostate dysplasia, increased proliferative activity, but did not induced changes on apoptosis, or Bcl-2 immunoreactivity. The addition of Zn did not modify the histological, immunohistochemical, and molecular features observed in the solely Cd-treated rats.

Figure 2. PCR-SSCA gels. There was no variation on the band pattern of the amplified segment of the bcl-2 gene in relation to the treatment. a: Samples after 6.0 mo, b: Samples after 18.0 mo. c: Samples after 12.0 mo. d: Samples after 12.0 mo.
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