In vivo and in vitro interaction of 1,2-dichlorobenzene with nucleic acids and proteins of mice and rats

Abstract

Twenty-two hours after i.p. injection into male Wistar rats and BALB/c mice, 1,2-dichlorobenzene (1,2-DCB) was covalently bound to DNA, RNA, and proteins of liver, kidney, lung and stomach. The covalent binding index to liver DNA was typical of carcinogens classified as weak initiators. The enzyme-mediated in vitro interaction of 1,2-DCB with calf thymus DNA of synthetic polyribonucleotides was carried out by a microsomal mixed-function oxidase system and microsomal GSH-transferases, which seemed to be effective only in liver and lung of rat and mouse. Cytosolic GSH-transferases played a minor role in 1,2-DCB bioactivation. The latter finding provides the first evidence of 1,2-DCB genotoxicity in mammalian cells. The type of halide, the number of halosubstituents and their spatial disposition on the benzene ring are the major determinants of halobenzenes activability to intermediate(s) capable of interacting covalently with DNA and other macromolecules in biologic systems.