IMPORTANCE OF SPECIES-DIFFERENCES IN EXPERIMENTAL PULMONARY CARCINOGENICITY OF INHALED CADMIUM FOR EXTRAPOLATION TO HUMANS

There is sufficient evidence for pulmonary carcinogenicity of inhaled cadmium (Cd) compounds in rats whereas no such evidence was found in m ice and hamsters, indicating significant species differences in the pu lmonary response to inhaled Cd. We hypothesized that expression of met allothionein (MT) protein in the lung after inhalation of Cd differs b etween species thereby providing different degrees of sequestration of Cd and protection from its effects. Rats and mice were exposed to 100 mu g CdCl2 aerosols/m(3) for 4 weeks, and the presence of MT was dete rmined in lung and free lung cell homogenates as well as by immunocyto chemistry in lung sections up to 28 days post-exposure. Cd exposure si gnificantly increased MT in homogenates of total lung in both species; however, no significant increase of MT in rat lung tissue after remov al of free lung cells by lavage was found whereas MT was still signifi cantly increased in lavaged mouse lung tissue throughout the post-expo sure time. Histochemical analysis of lung sections revealed that mainl y the epithelial cells of the bronchi, bronchioli and alveoli of Cd-ex posed mice expressed MT, Baseline MT levels were also greater in the l ungs of mice compared to rats, The retained Cd dose per g lung was abo ut I-fold greater in mice. The greater MT induction upon exposure to t he same inhaled Cd concentration and the greater baseline MT levels ma y offer an explanation for the resistance of mice towards the pulmonar y carcinogenic effect of inhaled Cd.