Formation of lipid adducts by carbon tetrachloride

Toxicity of carbon tetrachloride (CCl₄) is mediated by the formation of a trichloromethyl radical (·CCl₃) through one electron reduction by cytochrome P-450. The ·CCl₃ radical thus formed may undergo further transformation to reactive metabolites or may modify biomolecules. To elucidate the mechanism by which CCl₄ reacts with lipids, a benzoyl peroxide initiated free radical addition of CCl₄ to methyl oleate was studied. Methyl oleate adducts of CCl₄ were separated by high performance liquid chromatography into these fractions. Ammonia chemical ionization mass spectrometry and the 20 eV electron impact mass spectra of all three fractions indicated molecular weight of 448 and the presence of four chlorine atoms. Proton magnetic resonance spectroscopy indicated that fraction 1 is a mixture while fractions 2 and 3 are isomeric products from the addition of chlorine and trichloromethyl across the double bond of methyl oleate. This study demonstrates the structural complexity of lipids covalently modified by CCl₄. Formation of such adducts may alter membrane structure and function, and thus contriubte to the observed toxicity of CCl₄.