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Title: Covalent interaction of 3,3'-dichlorobenzidine with hepatic lipids. Enzymic basis and stability of the adducts.

Authors: Iba, M M; Lang, B; Thomas, P E; Ghosal, A

Published In Biochem Pharmacol, (1990 Aug 01)

Abstract: Administration of a single oral dose (20 mg/kg) of [U-14C]3,3'-dichlorobenzidine to rats resulted in the in vivo covalent binding of the compound to hepatic lipids. More than 70% of the lipid-3,3'-dichlorobenzidine adducts were accounted for in microsomes. Loss of the lipid-bound 3,3'-dichlorobenzidine residues from either total liver or endoplasmic reticulum occurred in at least two phases--an initial fast phase and a terminal slow phase. In vitro studies with hepatic microsomes in the presence of antibodies to specific P450 isozymes and chemical inhibitors to determine the enzymes that activate 3,3'-dichlorobenzidine to the lipid-binding derivative(s) implicated cytochrome P450d. The 3,3'-dichlorobenzidine-bound microsomal lipids were not mutagenic to Salmonella TA98 in the Ames test. The results suggest that adduct formation between 3,3'-dichlorobenzidine and membrane lipids may provide a measure of 3,3'-dichlorobenzidine activation. It is speculated that covalent interaction of the compound with membrane lipids may modify cellular processes, leading to either enhancement or attenuation of carcinogenesis by the chemical.

PubMed ID: 2116801 Exiting the NIEHS site

MeSH Terms: 3,3'-Dichlorobenzidine/metabolism*; 3,3'-Dichlorobenzidine/pharmacokinetics; 3,3'-Dichlorobenzidine/pharmacology; Animals; Antibodies/pharmacology; Benzidines/metabolism*; Biotransformation; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System/immunology; Cytochrome P-450 Enzyme System/metabolism; Endoplasmic Reticulum/metabolism; Isoenzymes/antagonists & inhibitors; Isoenzymes/immunology; Isoenzymes/metabolism; Lipid Metabolism*; Liver/enzymology*; Liver/ultrastructure; Male; Microsomes, Liver/enzymology; Mutagenicity Tests; NADPH-Ferrihemoprotein Reductase/immunology; NADPH-Ferrihemoprotein Reductase/metabolism; Oxygenases/antagonists & inhibitors; Oxygenases/metabolism; Rats; Rats, Inbred Strains

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