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Molecular Pharmacology, Vol 13, 698-705, Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics

The Reduction of Polyhalogenated Methanes by Liver Microsomal Cytochrome P450

C. ROLAND WOLF 1, DANIEL MANSUY 1, WOLFGANG NASTAINCZYK 1, GENEVIÈVE DEUTSCHMANN 1, and VOLKER ULLRICH 1

1 Department of Physiological Chemistry, University of the Saarland, 665 Homburg, Saar, German Federal Republic

Under anaerobic reducing conditions various polyhalogenated methanes (CBr4, CCl4, CCl3F, CCl3Br, CCl3CN, CHI3, CHBr3, and CHCl3) form complexes with ferrous cytochrome P450 with absorption peaks in the difference spectra ranging between 450 and 470 nm. Carbon monoxide was detected as a metabolic product of the interaction. Inhibition experiments indicated the involvement of cytochrome P450 in the reduction process, and a reaction sequence is proposed to account for these findings. Comparison of cytochrome P450 complex formation using liver microsomal preparations from phenobarbital- and 3,4-benzpyrene-treated rats showed differences which could be accounted for by decreased stability of the halogenomethane complex with the 3,4-benzpyrene-induced form of cytochrome P450.

Submitted on December 20, 1976
Accepted on March 9, 1977




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