Gower J D, Wills E D
Division of Comparative Medicine, Clinical Research Centre, Harrow, Middlesex, U.K.
Chem Biol Interact. 1987;63(1):63-74. doi: 10.1016/0009-2797(87)90105-0.
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.
本研究表明，大鼠小肠黏膜微粒体部分有能力通过涉及混合功能氧化酶系统（依赖烟酰胺腺嘌呤二核苷酸磷酸）的机制以及由于亚铁离子、抗坏血酸和二磷酸腺苷引发膜磷脂过氧化作用，将苯并[a]芘（BP）-7,8-二醇催化氧化为BP-二醇环氧化物（BPDEs）。依赖烟酰胺腺嘌呤二核苷酸磷酸的反应在小肠近端最快，导致生成大致等量的BPDE I和BPDE II。脂质过氧化催化反应有利于BPDE I的产生，在小肠中部区域最大，与肠段中脂质过氧化速率密切平行。用富含二十碳五烯酸和二十二碳六烯酸的鱼肝油日粮喂养大鼠，显著增加了这些脂肪酸掺入微粒体部分的量。这导致体外脂质过氧化速率大幅增加，与喂食无脂、单不饱和猪油或玉米油（58%十八碳二烯酸）日粮的大鼠相比，脂质过氧化催化的BP-7,8-二醇氧化速率显著更高。因此，在喂食多不饱和脂肪的大鼠肠道部分脂质过氧化过程中，BP-7,8-二醇向其最终致癌形式的转化速率，在体外测量时比依赖烟酰胺腺嘌呤二核苷酸磷酸催化的反应在数量上更重要。
