Cadmium Carcinogenicity and Genotoxicity

Abstract

Cadmium is a toxic transition metal of continuing occupational and environmental concern. Several reviews are available concerning various aspects of cadmium toxicity (IARC, 1976, 1993; Friberg et al., 1986a,b; Kazantzis, 1987; Waalkes and Oberdörster, 1990; Waalkes et al., 1992a). Cadmium has recently been designated a human carcinogen (IARC, 1993) and is clearly a potent animal carcinogen (IARC, 1976, 1994; Oberdörster, 1986; Waalkes and Oberdörster, 1990; Waalkes et al., 1992a). Occupational exposure to cadmium has been linked to lung cancers in humans, while at other sites, such as the prostate, linkage has not been definitively established (IARC, 1993; Waalkes and Oberdörster, 1990; Waalkes et al. 1992a). Several studies in rodents have shown that chronic inhalation of cadmium causes pulmonary carcinomas (Takenaka et al., 1983), in clear support of human data. Cadmium can also be a prostatic carcinogen after systemic or direct exposure (Waalkes et al., 1988a, 1989; Waalkes and Rehm, 1992; Hoffman et al., 1985a,b, 1988). Other target tissues of cadmium carcinogenesis in animals include injection sites (Heath et al., 1962; Kazantzis, 1963; Haddow et al., 1964), the testes (Gunn and Gould, 1970), and the hematopoietic system (Waalkes et al., 1992b, 1994; Waalkes and Rehm, 1992, 1994a,b). Certain treatments modify cadmium carcinogenicity, including administration of zinc, which prevents cadmium-induced injection site and testicular tumors while facilitating prostatic tumor formation (Gunn et al., 1963, 1964; Waalkes et al., 1989). Diets deficient in zinc increase the progression of testicular tumors (Waalkes et al., 1991a) but reduce the progression of prostatic tumors (Waalkes and Rehm, 1992). There are definite species- and strain-related differences in sensitivity to cadmium carcinogenicity (Heinrich et al., 1989; Waalkes et al., 1991b, 1994; Waalkes and Rehm, 1994a,b). The potential mechanism or mechanisms of cadmium carcinogenesis as yet are unknown but may well be target tissue specific.

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