Chronic Toxic and Carcinogenic Effects of Cadmium Chloride in Male DBA/2NCr and NFS/NCr Mice: Strain-Dependent Association with Tumors of the Hematopoietic System, Injection Site, Liver, and Lung

Abstract

Chronic Toxic and Carcinogenic Effects of Cadmium Chloride in Male DBA/2NCr and NFS/NCr Mice: Strain-Dependent Association with Tumors of the Hematopoietic System, Injection Site, Liver, and Lung. Waalkes, M.P., and Rehm, S. (1994). Fundam. Appl. Toxicol. 23, 21-31.

Although the acute toxic effects of cadmium in mice vary greatly with strain, relatively little is known about strain differences in cadmium carcinogenesis. Therefore, this work was performed to assess the chronic toxic and carcinogenic effects of cadmium in two strains of mice generally thought to be susceptible to the acute effects of cadmium. Male DBA/2NCr (DBA) and NFS/NCr (NFS) mice were given CdCl₂ (40 μmol/kg, sc) either as a single dose (1 × 40) or as weekly doses for 16 weeks (16 × 40) starting at 8 weeks of age. Controls received saline. The animals were observed for the next 104 weeks and mice at risk were defined as those surviving to the time of appearance of a particular tumor. Cadmium-induced dose-related increases in lymphoma (primarily follicular center cell) incidence (1 × 40, 11 cases/23 mice at risk; 16 × 40, 16/28) over control (7/27) in DBA mice but not in NFS mice. Only NFS mice receiving repeated cadmium injections (16 × 40) showed sarcoma development at the injection site (9/35), as no sarcomas occurred in control NFS mice or any group of DBA mice. On the other hand, cadmium-treated (16 × 40) NFS mice, but not DBA mice, had more hepatocellular adenomas and carcinomas (9/27) than control (1/15) but only at the high dose (16 × 40). More cadmium-treated NFS mice had pulmonary tumors than controls, but only at the lower dose (1 × 40). Although testicular tumors were rare, nonneoplastic lesions (fibrosis and mineralization) were induced by cadmium to a similar extent in both strains. Clearly cadmium carcinogenicity varies widely with strain, indicating a genetic basis to susceptibility. The basis of these strain differences deserves further study.