Strain-related differences in CYP2E1 levels are associated with differential bioactivation of 1,1-dichloroethylene in murine lung and liver

1,1-Dichloroethylene (DCE), a copolymer in the production of plastic food wrapping and flame-retardant fabrics, has been shown to be pneumotoxic and hepatotoxic. Previous investigations have ascribed these effects to metabolic activation of DCE to an epoxide by the cytochrome P450 monooxygenases, and principally the isozyme CYP2E1. In the present studies, we tested the hypothesis that strain-related variations in CYP2E1 levels determine the extent of DCE bioactivation and severities of cytotoxicity in lung and liver of A/J, CD-1 and C57BL/6 mice. We have also compared the levels of hepatic and pulmonary GSH in control and DCE-treated mice. Our results demonstrated that lungs and livers from A/J mice had the highest levels of CYP2E1, which was reflected in the levels of covalent binding detected, the formation of DCE-epoxide and the severity of cytotoxicity observed. On the contrary, lungs and livers obtained from C57BL/6 mice had the least amount of CYP2E1 expression. Furthermore, the levels of covalent binding, formation of metabolites and cytotoxicity in the lungs and livers of C57BL/6 mice were the lowest of the 3 strains examined. Levels of cellular GSH were consistent in all 3 strains before and after DCE treatment. Thus, the results of this study suggested that DCE bioactivation is associated mainly with CYP2E1 expression in murine liver and lung.