METALLOTHIONEIN INDUCTION AND PULMONARY RESPONSES TO INHALED CADMIUM CHLORIDE IN RATS AND MICE

Inhaled CdCl2 is a pulmonary carcinogen in rats but not in mice. We hy pothesized that pulmonary metallothionein (MT) induction may be differ ent in both species and thereby may lead to different levels of protec tion from Cd-induced lung injury. Fisher-344 rats and B6C3F, mice were exposed for 4 weeks to CdCl2 aerosols of 0, 30, 50, and 150 mu g/m(3) air or 0, 10, 30, and 100 mu g/m(3) air, respectively. Animals from e ach exposure group were terminated at 1, 30, and 133 days after the en d of exposure. The lungs were lavaged for cell and biochemical analyse s. Cadmium and MT in lavagate and lung tissue were measured. The reten tion half-time of pulmonary Cd was greater in mice (290 vs 90 days, p < 0.05). Cd exposure provoked an inflammatory response which was dose- dependent in both species, and while it was only short-lived in rats, it persisted throughout the observation period in mice at the high exp osure concentrations. Mice were found to have a greater baseline level of MT (18.04 +/- 6.96 vs 11.7 +/- 1.98 mu g MT/g control lung, p < 0. 05). Mice showed greater inducibility of MT for a given CdCl2 exposure concentration; however, both species had a similar relationship betwe en retained pulmonary Cd and MT induction though mice maintained incre ased MT levels for a longer period of time. The greater pulmonary base line MT together with the longer presence of Cd-induced pulmonary MT m ay result in greater protection from Cd carcinogenicity in spite of th e greater pulmonary Cd-induced inflammation in mice. (C) 1996 Society of Toxicology