Tumorigenesis by cadmium.

Abstract

A single dose of cadmium chloride (CdCl2) (0.02–0.03 mM/kg) given subcutaneously to mature male Wistar rats leads to rapid testicular necrosis and, subsequently, to the development of interstitial cell neoplasms. Testicular tissue containing these neoplasms transforms labeled progesterone in vitro to testosterone, but this transformation is less efficient than that by normal testicular tissue. The interstitial cell tumors develop slowly; the first indications of interstitial cell proliferation are noted 48 days after cadmium injection. Uptake studies with labeled isotopes (109Cd and 65Zn) indicate that Cd in the testes reaches a maximum within 6 h after subcutaneous injection, whereas 65Zn, in contrast, is deposited continuously for at least 20 days. Although the concentration of cadmium in the testes is markedly lower than in the liver, kidneys, or at the site of cadmium injection, tumorigenesis in the testes appears to be linked to the specific, acute toxic action of Cd++ on the testes, perhaps via the injury to the vessels, and the subsequent process of cell regeneration. Following a subcutaneous injection of CdCl2 it was rapidly absorbed, but at the site of injection (skin, subcutaneous tissue, fascia and muscle) a higher concentration of Cd was retained than that found in other areas of connective tissues. In rats injected with 0.03 mM CdCl2 subcutaneously the site of injection showed at later periods calcification, fibrosis, and in two instances, fibrosarcoma. The abnormal tissue reaction and tumorigenesis at the site of injection is attributed to Cd fixation to the traumatized connective tissue. Injections of CdCl2 directly into the liver were also followed by testicular necrosis. So far no hepatic tumors following the injection have been encountered.