Microsomal bioactivation and covalent binding of aliphatic halides to DNA

Studies were carried out on the in vitro covalent binding of a series of 14C-labeled aliphatic halides to calf thymus DNA following bioactivation by hepatic microsomes isolated from phenobarbital-treated rats. Six compounds were shown to exhibit binding to DNA of greater than 0.3 nmol/mg DNA (1,2-dibromoethane, bromotrichloromethane, trichloroethylene, carbon tetrachloride, chloroform, and 1,1,2-trichloroethane). Covalent binding of the aliphatic halides to the nucleic acids was confirmed by sedimentation of the DNA-organohalogen adduct in a cesium chloride gradient and Sephadex LH-20 chromatography of the nucleosides released by enzymatic hydrolysis.