et al., 1985; NTP, 1993; Nikula et al., 1995;Heinrich et al., Inhaled CdCl 2 is a pulmonary carcinogen in rats but not in mice. 1995). Different strains of rats and mice have been used We hypothesized that pulmonary metallothionein (MT) induction in the different studies with cadmium and solid particles, may be different in both species and thereby may lead to different including the standard strains for chronic NTP bioassays, levels of protection from Cd-induced lung injury. Fisher-344 rats and i.e., Fischer-344 rats and B6C3F 1 mice. The species-specific B6C3F 1 mice were exposed for 4 weeks to CdCl 2 aerosols of 0, 30, lung tumor response was found in all of them and we de- cided, therefore, to use those standard strains in our subseAnimals from each exposure group were terminated at 1, 30, and quent studies. With respect to particle-induced lung tumors 133 days after the end of exposure. The lungs were lavaged for cell in rats, a condition of lung particle overload is thought to and biochemical analyses. Cadmium and MT in lavagate and lung tissue were measured. The retention half-time of pulmonary Cd was be the basis (Oberdörster, 1995), yet this condition does not greater in mice (290 vs 90 days, p õ 0.05). Cd exposure provoked occur after low-level Cd exposure. Thus, the reasons for an inflammatory response which was dose-dependent in both species, these species differences in tumorigenic response to inhaled and while it was only short-lived in rats, it persisted throughout the Cd are not known yet and studying them provides a unique observation period in mice at the high exposure concentrations. Mice opportunity to gain a better understanding of the mechanisms were found to have a greater baseline level of MT (18.04 { 6.96 vs important for Cd carcinogenesis, which may include species 11.7 { 1.98 mg MT/g control lung, p õ 0.05). Mice showed greater differences in metallothionein (MT) induction and turnover.
inducibility of MT for a given CdCl 2 exposure concentration; how-MT is a low-molecular-weight protein which is highly ever, both species had a similar relationship between retained pulmoconserved throughout the animal kingdom. The major role nary Cd and MT induction though mice maintained increased MT levels for a longer period of time. The greater pulmonary baseline of MT appears to be its involvement with essential metal MT together with the longer presence of Cd-induced pulmonary MT homeostasis, specifically its physiologic association with may result in greater protection from Cd carcinogenicity in spite of zinc and copper metabolism. It has also been suggested that the greater pulmonary Cd-induced inflammation in mice. ᭧ 1996 MT plays a role in protecting cells from heavy metal toxicity
Society of Toxicology(e.g., Cd, Hg) and oxidant stresses and, moreover, that MT may protect cells from the carcinogenic effect of Cd by sequestering Cd. The reader is referred to several reviews Inhaled cadmium (Cd) has been linked with lung cancer in for further details of the role of MT with respect to heavy human...