The role of lipid peroxidation in the N-oxidation of 4-chloroaniline.
Irradiation with u.v. light of aerobic aqueous media containing both rabbit liver microsomal fraction and 4-chloroaniline results in N-oxidation of the arylamine. The reaction is severely blocked by exhaustive extraction with organic solvents of the microsomal membranes to remove lipids. Further, scavengers of OH. and O2.-impair the photochemical process. These findings suggest that the observed phenomenon may be closely associated with light-induced lipid peroxidation. Indeed, N-oxidation of 4-chloroaniline is fully preserved when either phospholipid liposomes or dispersed linoleic acid substitute for intact microsomal fraction. Co-oxidation of the amine substrate occurs during iron/ascorbate-promoted lipid peroxidation also, but H2O2 or free OH. radicals do not appear to be involved. Cumene hydroperoxide-sustained rabbit liver microsomal turnover of the amine generates N-oxy product via O2-dependent and -independent pathways; propagation of lipid peroxidation is presumed to govern the former route. Lipid hydroperoxides, either exogenously added to rabbit liver microsomal suspensions or enzymically formed from arachidonic acid in ram seminal-vesicle microsomal preparations, support N-oxidation of 4-chloroaniline. The significance, in arylamine activation, of lipid peroxidation in certain extrahepatic tissues exhibiting but low mono-oxygenase activity is discussed.
D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001555:Benzene Derivatives / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008027:Light; D050356:Lipid Metabolism; D008054:Lipid Peroxides / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D011817:Rabbits
D000814:Aniline Compounds; D001555:Benzene Derivatives; D008054:Lipid Peroxides; D008081:Liposomes; C007164:cumene hydroperoxide; D001205:Ascorbic Acid; C004658:4-chloroaniline