| 6870950 |
McCall SN, Jurgens P, Ivanetich KM: Hepatic microsomal metabolism of the dichloroethanes. Biochem Pharmacol. 1983 Jan 15;32(2):207-13.
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. |
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