Jj. Martin et al., Cadmium chloride-induced dysplastic changes in the ventral rat prostate: An immunohistochemical and quantitative study, PROSTATE, 46(1), 2001, pp. 11-20
BACKGROUND. Cadmium chloride is an environmental toxic that might be implic
ated in human prostate carcinogenesis. The study was directed: 1) to evalua
te the immunoexpression of markers for cell proliferation, apoptosis, and r
esistance to apoptosis, and 2) to estimate the size of premalignant cell po
pulation in the preneoplastic changes induced in ventral prostates of rats
treated with cadmium chloride administered in drinking water.
METHODS. The following parameters were calculated in the ventral prostatic
lobe of normal rats and rats that received cadmium in drinking water during
18 months: total volume, epithelial volume, total number of epithelial cel
ls, numerical density of epithelial cells, percentage of cells that immunos
tained to the proliferating cell nuclear antigen (PCNA), percentage of apop
totic cells (evaluated by a DNA fragmentation method), and absolute volume
and volume fraction of immunostaining to bcl-2.
RESULTS. The percentage of PCNA immunoreactive nuclei, the bcl-2 expression
, and the numerical density of epithelial cells were significantly (P < 0.0
5) increased in the dysplastic prostatic acini of treated rats in compariso
n with the normal acini of treated rats and control animals. The percentage
of apoptotic nuclei from ventral dysplastic acini was significantly (P < 0
.05) decreased in comparison with that of normal acini. A negative correlat
ion between proliferation and apoptosis was found in dysplastic lesions.
CONCLUSIONS. Prostate epithelial dysplasia induced in rats by cadmium prese
nts an increased proliferative activity and high expression of bcl-2 protei
n, as was described in human prostate intraepithelial neoplasia. However, t
he rate of apoptosis in rat dysplasia was importantly decreased, in contras
t to that observed in some human preneoplastic changes. This decrease might
be related to the increase of bcl-2 expression. Prostate 46:11-20, 2001. (
C) 2001 Wiley-Liss, Inc.