The oxidation of benzo[a]pyrene-7,8-dihydrodiol mediated by lipid peroxidation in the rat intestine and the effect of dietary lipids.
This study has demonstrated that the microsomal fraction of the rat small intestinal mucosa has the capacity to catalyse the oxidation of benzo[a]pyrene(BP)-7,8-diol to BP-diol-epoxides (BPDEs) both by a mechanism involving the mixed-function oxidase system (NADPH-dependent) and as a result of the initiation of peroxidation of the membrane phospholipids by ferrous ions, ascorbate and ADP. The NADPH-dependent reaction was fastest in the proximal part of the intestine and resulted in the formation of approximately equal amounts of BPDE I and BPDE II. The lipid peroxidation-catalysed reaction favoured the production of BPDE I and was maximal in the middle region of the intestine, closely paralleling the rate of lipid peroxidation in the intestinal sections. Feeding rats on a cod liver oil diet, rich in C20:5 and C22:6, significantly increased the incorporation of these fatty acids into the microsomal fractions. This resulted in a greatly increased rate of lipid peroxidation in vitro and a significantly higher rate of lipid peroxidation-catalysed BP-7,8-diol oxidation compared to rats fed fat-free, mono-unsaturated lard or corn oil (58% C18:2) diets. Thus the rate of conversion of BP-7,8-diol to its ultimate carcinogenic forms during lipid peroxidation in the intestinal fractions of rats fed a polyunsaturated fat was quantitatively more important than the NADPH-catalysed reaction as measured in vitro.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003060:Cod Liver Oil / Q000494:pharmacology; D003314:Corn Oil / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology*; D004101:Dihydroxydihydrobenzopyrenes / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009249:NADP / Q000494:pharmacology; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
D004041:Dietary Fats; D004101:Dihydroxydihydrobenzopyrenes; D005227:Fatty Acids; D008054:Lipid Peroxides; C017228:benzo(a)pyrene 7,8-dihydrodiol; D009249:NADP; D003314:Corn Oil; D003060:Cod Liver Oil; D006899:Mixed Function Oxygenases; C029310:lard