Cadmium chloride-induced dysplastic changes in the ventral rat prostate: an immunohistochemical and quantitative study.
BACKGROUND
Cadmium chloride is an environmental toxic that might be implicated in human prostate carcinogenesis. The study was directed: 1) to evaluate the immunoexpression of markers for cell proliferation, apoptosis, and resistance to apoptosis, and 2) to estimate the size of premalignant cell population 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 cells, numerical density of epithelial cells, percentage of cells that immunostained to the proliferating cell nuclear antigen (PCNA), percentage of apoptotic 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 < 0.05) increased in the dysplastic prostatic acini of treated rats in comparison 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 correlation between proliferation and apoptosis was found in dysplastic lesions.


CONCLUSIONS
Prostate epithelial dysplasia induced in rats by cadmium presents an increased proliferative activity and high expression of bcl-2 protein, as was described in human prostate intraepithelial neoplasia. However, the rate of apoptosis in rat dysplasia was importantly decreased, in contrast to that observed in some human preneoplastic changes. This decrease might be related to the increase of bcl-2 expression.
Martín
J J
JJ
Department of Anaesthesiology, Hospital Ramón y Cajal, Madrid, Spain.
Martín
R
R
Codesal
J
J
Fraile
B
B
Paniagua
R
R
Santamaría
L
L
D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D053938:DNA Fragmentation; D004848:Epithelium / Q000473:pathology; D019254:Genes, bcl-2; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011467:Prostate / Q000187:drug effects / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D019256:Cadmium Chloride