Cadmium Neoplasia: Testicular Atrophy and Leydig Cell Hyperplasia and Neoplasia in Rats and Mice Following the Subcutaneous Injection of Cadmium Salts

Abstract

IN an accompanying paper the induction of sarcomata at the site of repeated subcutaneous injection into rats of cadmium sulphate, or of cadmium-precipitated rat-ferritin, is described, and the failure to induce such tumours in mice by similar treatment reported (Haddow et al., 1964). In the present paper the occurrence of testicular lesions and of pituitary changes in cadmium-treated rats and mice is described and discussed.For some time it has been known that cadmium is highly toxic to the testes of a number of animals. Parizek and Zahor (1956) reported complete necrosis of the testes of rats given one subcutaneous injection of cadmium chloride in a dose as small as 0.02 millimole per kilogram of body weight. They obtained similar results in mice, rabbits, guinea pigs and golden hamsters. This work has since been confirmed by a number of other workers, including Meek (1959), using mice.Kar and Das (1960) studied the sequence of events after a cadmium chloride injection in rats and noticed intense va'scular congestion of the testis within six hours. After two days the seminiferous epithehum was completely destroyed and transformed into a mass of debris. The changes in the interstitium, which they described as being of " similar magnitude ", resulted within two to seven days in total loss of anatomical structure and functional activity. The present authors obtained similar results in male rats using a single subcutaneous injection of cadmium, sulphate (Cd S04-4H20) in doses varying from 0.5 to 2-0 mg. per 100 g. body weight (equivalent to 0.2 to 0-8 mg. per 100 g. cadmium).A number of reports have commented upon the return of androgenic activity to testes rendered necrotic by cadmium and have described proliferation beneath the tunica albuginea of fibroblast-like cells which later show the typical structure of Leydig ceRs.The

Rodent Leydig Cell Tumorigenesis: A Review of the Physiology, Pathology, Mechanisms, and Relevance to Humans

“…These and later findings showing that cadmiuminduced testicular atrophy in rats and mice resulted in a high incidence of LCTs (Roe, 1964) fostered the belief that any form of seminiferous tubule damage resulted in an increase in LC number. Studies involving induction of focal damage to the seminiferous tubules of rats (Aoki and Fawcett, 1978) reinforced this belief.…”

High frequency of metalworkers among patients with seminomatous tumors of the testis: A case‐control study

“…Similar tumor risks are rather difficult to confirm in men, where mainly the linkage of cancer of the respiratory system with an exposure to chromium and nickel dusts is established. An unusual proportion of metalworkers were found among patients with sarcomas [Ott and Frey, 19611, carcinoma of the pancreas [Dorken, 1964;Maruchi et al, 19791, scrota1 carcinomas [Roush et al, 19821, and sinonasal carcinomas [Roush et al, 19801. Regarding tumors of the testis, it is of interest that mainly metallic compounds (especially cadmium and zinc salts) were successfully used for tumor induction in animals [Gunn et al, 1964;Roe et al, 1964;Guthrie, 1964;Dvizhkov and Potapova, 19701. Parizek and Zahor [1956] first recognized the damaging effect of cadmium salts on testicular tissue.…”

Cadmium and prostate cancer

“…In this and subsequent Downloaded by [Cornell University Library] at 21:37 19 November 2014 studies, cadmium produced sarcomas at the site of im or sc injection and testicular interstitial cell tumors and/or proliferations (Heath et al, 1962;Gunn et al, 1963Gunn et al, , 1964Haddow et al, 1964;IARC, 1976;Roe et al, 1964). Early efforts concerning mechanisms revealed the ability of zinc to protect against the necrotizing and carcinogenic effects of cadmium within the testes (Gunn et al, 1963(Gunn et al, , 1964.…”