1,1,2-Trichloroethane: evidence of genotoxicity from short-term tests.
At 22 hr after ip injection into adult male Wistar rats, 1,1,2-trichloroethane was covalently bound to DNA, RNA and proteins of the liver, kidney, lung and stomach, as has been found with various weakly carcinogenic halo compounds. The extent of interaction of 1,1,2-trichloroethane with mouse liver DNA was much higher than that with rat liver DNA. This result provides evidence of a correlation between adducts formation and species susceptibility to hepatocarcinogenesis (only the mouse is sensitive to the oncogenic effect of this compound). Interaction with DNA mediated by murine liver microsomes occurred in vitro. No particular differences between the two species were found. In vitro binding was enhanced (approximately 5-fold) by pretreatment in vivo with phenobarbitone but was suppressed by addition of 2-diethylamino-ethyl-2,2-diphenylvalerate X HCl in vitro. Cytochrome P-450 was, therefore, involved in the interaction process. Glutathione suppressed the microsome-mediated interaction, acting as a "scavenger" of reactive intermediate(s). Murine lung microsomes were less effective bioactivators than liver microsomes for the interaction with DNA and microsomal RNA, but not microsomal protein. Kidney and stomach microsomes were ineffective, as were cytosolic fractions from all of the assayed organs of the two species. The extent of in vitro interaction of 1,1,2-trichloroethane with synthetic polyribonucleotides was of the same order of magnitude as that with DNA. The results represent further clear evidence for genotoxicity of 1,1,2-trichloroethane.
D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D004247:DNA / Q000378:metabolism*; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008861:Microsomes / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014240:Trichloroethanes / Q000378:metabolism* / Q000633:toxicity
D006843:Hydrocarbons, Chlorinated; D009153:Mutagens; D014240:Trichloroethanes; C024567:1,1,2-trichloroethane; D012313:RNA; D004247:DNA; D003577:Cytochrome P-450 Enzyme System