Quinone formation from carcinogenic benzo[a]pyrene mediated by lipid peroxidation in phosphatidylcholine liposomes.
The behavior of benzo[a]pyrene (B[a]P) during peroxidation of phosphatidylcholine (PC) liposomes initiated by an azo compound was investigated to examine the mechanism of quinone formation from carcinogenic B[a]P mediated by nonenzymatic lipid peroxidation occurring in vivo. B[a]P had a retarding effect on the peroxidation of polyunsaturated fatty acid moiety of PC. The major oxidation products which accumulated in the peroxidized liposomes were B[a]P 1,6-, 3,6-, and 6,12-quinone. Antioxidants acting as scavengers of chain-propagating lipid peroxy radicals effectively prevented not only lipid peroxidation but also B[a]P oxidation in the liposomal suspension. PC hydroperoxides, the primary products of PC oxidation, did not react with B[a]P in the absence of the azo compound, indicating that lipid peroxy radicals, not lipid hydroperoxides, are responsible for the formation of these quinones. The experiments using 18O2 gas and 18O-labeled methyl linoleate hydroperoxides demonstrated that B[a]P quinones are formed by incorporating molecular oxygen and their origin is partly due to the lipid peroxy radical. The mechanism proposed for the formation of B[a]P quinones mediated by peroxidation of membrane lipids involves a direct attack of the lipid peroxy radical on B[a]P and subsequent autocatalytic oxidation. Weak carcinogenic and noncarcinogenic pentacyclic aromatic hydrocarbons showed little reactivity to the lipid peroxy radical in the liposomes. Thus, the facility of the peroxidative attack on B[a]P may be related to the powerful carcinogenic activity of this substance.
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D008054:Lipid Peroxides / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism*; D008099:Liver / Q000032:analysis; D008297:Male; D010103:Oxygen Isotopes; D010713:Phosphatidylcholines / Q000378:metabolism*; D011809:Quinones / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D008054:Lipid Peroxides; D008081:Liposomes; D010103:Oxygen Isotopes; D010713:Phosphatidylcholines; D011809:Quinones; C008464:methyl linoleate hydroperoxide; D001564:Benzo(a)pyrene