Carcinogenic effects of cadmium on the prostate of the rat

Abstract

The carcinogenic effects of cadmium were tested in an animal experiment to check the results of epidemiological studies showing that the incidence of prostatic carcinoma is above average in workers industrially exposed to high cadmium levels. For this purpose 1.9 mg CdCl2 (1.2 mg Cd/kg body weight) was injected into the right ventral prostatic lobe of 12-month-old male inbred rats of the Okamoto-toki strain. Simple hyperplasia was found in 38, atypical hyperplasia in 29, atypical hyperplasia with severe dysplasia in 11 and invasive prostatic carcinoma in 5 of 100 animals 270 days after the injection. Various mechanisms are discussed in connection with the carcinogenic action of cadmium.

Cadmium and prostate cancer

“…Interestingly, the primary cultures of rat ventral prostatic epithelial cells were highly sensitive to cadmium cytotoxicity prior to transformation. These findings are consistent with chronic rodent studies that uniformly show the ventral prostate as the target site for cadmium induction of prostatic tumors (Waalkes et al, 1988Waalkes & Rehm, 1992;Hoffmann et al, 1985aHoffmann et al, , 1985bHoffmann et al, , 1988Shirai et al, 1993b). Primary cultures of human prostatic epithelium did not undergo cadmium-induced transformation, although these samples were from abnormal tissues (BPH) obtained by prostatectomy (Terracio & Nachtigal, 1986).…”

“…A total of 17/207 (8.2%) of the rats directly injected in the prostate developed prostatic tumors, generally carcinomas. In addition to the lack of controls, this study has many flaws, not the least of which is the fact that when Hoffmann et al (1985aHoffmann et al ( , 1985b attempted to duplicate these results they found the doses of cadmium used to be invariably lethal in rats.…”

“…In much more carefully conducted experiments, Hoffmann et al (1985aHoffmann et al ( , 1985b injected rats with 0.44 mg Cd/rat as cadmium chloride in saline into the right lobe of the ventral prostate. Twenty saline-injected rats of the same age served as controls and animals were observed for the next 9 mo.…”

Epidemiological and experimental aspects of metal carcinogenesis: physicochemical properties, kinetics, and the active species.

“…Zinc acetate in a dose of 1 mmole/kg changed the target of SC CdCl2 from the testis to the prostate, but it decreased the incidence ofprostatic adenomas from 42 % to 25 % after the IM administration ofcadmium (105). Carcinomas in the prostate were produced in rats only rarely when 1.2 mg Cd/kg as CdCl2 was injected into the ventral prostate (106).…”

Cancer risk from inorganics

“…Chronic low level dietary exposure to cadmium has proven negative, as have the several earlier experiments on rodents designed to investigate the relationship of cadmium to cancer of the prostate [96]. The induction of prostatic carcinomas in the rat has recently been achieved by the injection of CdCI 2 into the ventral prostate lobe [97]. Five of 100 onc year-old rats developed prostate invasive carcinomas within 270 days of injection, 11 more developed an atypical hyperplasia with severe dysplasia, and 67 others showed less severe hyperplasias.…”