Expression of metallothionein protein in the lungs of Wistar rats and C57 and DBA mice exposed to cadmium oxide fumes

Chronic exposure to inhaled cadmium (Cd) has been shown to induce lung tumo rs in rats (Wistar strain) but not in mice (NMRI strain). The protein metal lothionein (MT) plays an important role in Cd detoxification, and it has be en suggested that differential inducibility of pulmonary MT may lead to int erspecies susceptibility differences to inhaled Cd. Interstrain differences in the pulmonary response of the MT gene to Cd stimuli have not been exami ned in rats or mice. We compared pulmonary MT expression in Wistar Furth (W F) rats with that in DBA and C57 mice, following a single 3-h exposure to C dO fumes containing 1 mg Cd/m(3). Induction of the MT gene was assessed by the levels of MT-I and MT-II transcripts, MT-protein content, and number of MT-labeled alveolar and bronchiolar epithelial cells immediately after Cd exposure and 1, 3, and 5 days later. Control animals were exposed to air/ar gon furnace gases. We observed differential intra- and interspecies inducib ility of the MT gene in the lung following Cd inhalation. DBA mice exhibite d greater levels of MT-mRNA, mainly for the MT-I isoform, MT-protein conten t, and number of MT positive cells relative to C57 mice. WF rats showed low er transcription and translation responses of the MT gene upon Cd stimuli t han C57 mice. The present results, in concert with our previous findings of higher lung cell proliferation in Cd-exposed C57 relative to DBA mice, pre dict greater susceptibility of C57 to the carcinogenic effects of inhaled C d. Furthermore, the low transcriptional and translation responses of the MT gene to Cd stimuli in WF rats might explain the higher susceptibility of t his rat strain to develop malignant lung tumors after chronic exposure to C d via inhalation. Parallel to our findings in mice, differences in the resp onsiveness of lung MT gene may exist across rat strains. Thus intraspecies genetic variability in pulmonary MT may influence the susceptibility of rat s or mice to lung carcinogenesis induced by inhalation of Cd compounds, (C) 1998 Academic Press.