Microsome-mediated covalent binding of 1,2-dichloroethane to lung microsomal protein and salmon sperm DNA

Abstract

In order to determine whether the covalent binding of the carcinogen 1,2-dichloroethane to macromolecules is dependent on microsomes or cytosol, microsomes and cytosol from lungs of C57BL/6 X C3H/He F1 (hereafter called B6C3F1) mice and Osborne-Mendel rats were incubated with [1,2-14C]dichloroethane and salmon sperm DNA. 1,2-Dichlorothane binds covalently to microsomal protein and DNA only in the presence of microsomes, whereas cytosol has insignificant metabolic activation. The binding to macromolecules was significantly higher in the presence of native microsomes than denatured microsomes. The interaction of 1,2-dichloroethane with DNA was enhanced following pretreatment of the animals with phenobarbital and 3-methylcholanthrene. On the other hand, glutathione reduced the binding. The binding of 1,2- dichloroethane to lung microsomal protein of B6C3F1 mice and to DNA was three and five times higher, respectively, than that of Osborne-Mendel rat lung microsomal proteins. 1,2-Dichloroethane interacts 85% and 100% more with protein and DNA, respectively, in the presence of microsomes obtained from lung than from liver of B6C3F1 mice. These results suggest a correlation between the microsomally mediated binding and species and organ susceptibility to 1,2-dichloroethane-induced tumorigenesis.