title: Hepatic microsomal metabolism of the dichloroethanes.
abstract: The binding of 1,1-dichloroethane (1,1-DCE) to the substrate binding site of hepatic microsomal cytochrome P-450, and the stimulation of hepatic microsomal CO-inhibitable NADPH oxidation by 1,1-DCE and 1,2-dichloroethane (1,2-DCE) were enhanced by induction with phenobarbital but not with beta-naphthoflavone. Incubation of the dichloroethanes with hepatic microsomes from phenobarbital-treated rats, NADPH-generating system and EDTA resulted in the conversion of 1,1-DCE to acetic acid and to a lesser extent to 2,2-dichloroethanol and probably also mono- and dichloroacetic acid and the conversion of 1,2-DCE to chloroacetaldehyde and to a lesser extent to chloroacetic acid and probably 2-chloroethanol. In addition, reaction mixtures constituted as described above resulted in slight but significant losses (ca. 13%) of hepatic microsomal cytochrome P-450. The omission of dichloroethane or the NADPH-generating system from incubation mixtures eliminated the above effects, and SKF-525A or CO diminished or eliminated the effects. Pathways for the metabolism of 1,1-DCE and 1,2-DCE are proposed.
mesh_terms: D000818:Animals; D002273:Carcinogens; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004000:Dichloroethylenes / Q000378:metabolism; D005025:Ethylene Dichlorides / Q000378:metabolism* / Q000633:toxicity; D006843:Hydrocarbons, Chlorinated / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009153:Mutagens; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats
chemical_list: D002273:Carcinogens; D004000:Dichloroethylenes; D005025:Ethylene Dichlorides; D006843:Hydrocarbons, Chlorinated; D009153:Mutagens; C029297:vinylidene chloride; D009249:NADP; C024565:ethylene dichloride; D003577:Cytochrome P-450 Enzyme System