Binding of trichloromethyl radicals to lipids of the hepatic endoplasmic reticulum during tetrachloromethane metabolism.

Metabolism of tetrachloromethane (carbon tetrachloride) by liver microsomal fraction under anaerobic conditions and in vivo leads to covalent binding of trichloromethyl radicals to lipids. The resulting covalently modified lipids contain two different types of fatty acids: a group of monomeric trichloromethyl fatty acid residues, usually with one double bond less than the precursor fatty acids, and a group of fatty acids that are not sufficiently volatile for gas chromatography. The liquid-chromatographic properties of the latter indicate high molecular mass, presumably due to cross-linking. The chemical structures of the monomeric fatty acids were elucidated, and these support the view that the most significant reactive metabolite of tetrachloromethane is the trichloromethyl radical. The isomer patterns of the monomeric trichloromethyl fatty acids in vitro and in vivo are almost identical, which shows that anaerobic incubation of tetrachloromethane with microsomal fraction very well reflects the processes involved in hepatotoxicity of tetrachloromethane in vivo.