The formation of mutagenic derivatives of benzo[a]pyrene by peroxidising fatty acids.
Benzo[a]pyrene (B[a]P) when incubated in the presence of peroxidising polyunsaturated fatty acids such as linoleic acid (C18:2), arachidonic acid (C20:4), eicosapentaenoic acid (C20:5) or docosahexaenoic acid (C22:6) was converted to oxidised products. Between 7% and 9% of the B[a]P was oxidised in one hour when incubated with arachidonic acid and docosahexaenoic acid. 1,6- 3,6- and 6,12-Quinone derivatives of B[a]P were identified by HPLC. The products of B[a]P oxidation were shown to be mutagenic when tested using Sister chromatid exchange (SCE) technique and the occurrence of SCEs in CHV79 cells was increased significantly. Lipid peroxides also induced SCEs in the absence of B[a]P and there was a positive correlation between the frequency of SCEs and the extent of lipid peroxidation. The results indicate that the oxidation of B[a]P mediated by the non-enzymic peroxidation of polyunsaturated fatty acids is likely to play a role in mutagenesis and, possibly, also in carcinogenesis.
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism*; D010084:Oxidation-Reduction; D012486:Salmonella typhimurium / Q000235:genetics; D012854:Sister Chromatid Exchange / Q000187:drug effects
D005231:Fatty Acids, Unsaturated; D008054:Lipid Peroxides; D009153:Mutagens; D001564:Benzo(a)pyrene