Cadmium carcinogenesis in male Wistar [Crl:(WI)BR] rats: dose-response analysis of tumor induction in the prostate and testes and at the injection site.

Carcinogenic dose-response effects of CdCl2 in male Wistar [Crl:(WI)BR] rats were studied over a 2-year period. Groups of rats received a single s.c. injection of CdCl2 at doses of 0, 1.0, 2.5, 5.0, 10.0, 20.0, or 40.0 mumol/kg in the dorsal thoracic midline. Other groups received either four separate s.c. doses of 5 mumol Cd/kg each (at 0, 48, 96, and 168 h), or low dose cadmium (5.0 mumol/kg, s.c., at 0 h) followed by a higher dose (10.0 or 20.0 mumol/kg, s.c., at 48 h). The cadmium treatments resulted in appearance of tumors at the injection site, in the testes, and in the ventral prostate. Injection site tumors (mostly sarcomas) appeared to be strictly related to accumulated dose of cadmium and approached a 45% incidence at the highest cadmium dose (40 mumol/kg). Testicular tumors (mostly Leydig cell adenomas) were found to be highly dependent on testicular degeneration caused by cadmium. The highest Leydig cell tumor incidence occurred in the 40 mumol/kg (83%) and 20 mumol/kg (72%) dosage groups. Low dose pretreatment (5.0 mumol/kg) reduced or prevented the testicular degeneration and tumor formation that would otherwise result from a subsequent higher dose of CdCl2 (20 mumol/kg). Prostatic tumors (mostly adenomas of the ventral lobe) were also found to be associated with cadmium treatment, but in a non-dose related fashion. Prostatic tumor incidence was significantly elevated at the 2.5 mumol/kg dose of CdCl2 (eight tumors/26 rats; 31%) and showed a strong positive correlation between 0.0 and 2.5 mumol/kg in both tumor incidence and multiplicity. At higher doses, including those that caused marked testicular degeneration and induced prostatic atrophy, an elevated incidence of tumors did not occur. The occurrence of hyperplastic foci of the prostate, however, showed a strong positive correlation with increasing dose after single injections of cadmium up to and including 20.0 mumol/kg. Results indicate that CdCl2 can induce preneoplastic lesions of the prostate that appear to develop into tumors only at doses well below those causing marked degeneration of the testes and atrophy of the prostate.