The kinetics of benzo(a)pyrene anti-7,8-dihydrodiol 9, 10-epoxide formation from benzo(a)pyrene and regulatory membrane effects.
The kinetics of benzo(a)pyrene anti-7,8-dihydrodiol 9, 10-epoxide formation from benzo(a)pyrene and regulatory membrane effects.
复制标题
苯并（a）芘抗7,8-二氢二醇9, 10-环氧化物形成苯并（a）芘的动力学和调节膜效应。
DOI：
10.1016/0003-9861(82)90247-8
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发表时间：
1982
影响因子：
3.9
通讯作者：
Fahl,WE
中科院分区：
文献类型：
--
作者：
Fahl,WE
用高效液相色谱法分离测定了诱导大鼠肝微粒体和BP孵育液的有机提取物中r-7，c-10，t-8，t-9-四羟基苯并（a）芘（7，10/8，9-tetrol）的含量，它是r-7，t-8-dihydroxy-t-9，10-oxy-7，8，9，10-tetrahydrobenzo（a）pyrene（anti-diol-epoxide）的主要水解产物。动力学分析表明：（a）在5- 7分钟的滞后期后，抗二醇-环氧化物的形成呈线性，（B）形成的抗二醇-环氧化物的水平高度依赖于起始BP浓度，在起始BP浓度为0-12 μmBP时，抗二醇-环氧化物的产生增加，在含有12-25 μmBP的孵育液中，抗二醇-环氧化物的产生减少。然而，在25至100 μmBP之间，抗二醇-环氧化物形成稳定在代表峰值产生的65%的水平，该峰值产生发生在12 μm的起始BP浓度下。（−）-trans-BP-7，8-dihydrodiol竞争性抑制BP氧化，而（+）-trans-BP-7，8-dihydrodiol的抑制效果约为前者的5倍。几倍过量的BP（25-100 μm）不能完全抑制BP-7，8-二氢二醇氧化，这是由于存在仅在6-8 μmBP饱和的微粒体底物室，剩余的BP以聚集体形式存在于水室中。与[3 H]BP反应后通过Sepharose 2B凝胶过滤纯化微粒体也表明BP-7，8-二氢二醇优先浓缩在微粒体室中，导致微粒体室中BP-7，8-二氢二醇与BP的比率净增加，这有利于BP-7，8-二氢二醇氧化产生生物活性的抗二醇环氧化物。
r-7,c-10,t-8,t-9-Tetrahydroxybenzo(a)pyrene (7,10/8,9-tetrol), which is the principal hydrolysis product ofr-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (anti-diol-epoxide), was resolved and measured by HPLC in organic extracts of incubations which contained induced rat liver microsomes and BP. Kinetic analyses showed that: (a) following a 5- to 7-min lag period,anti-diol-epoxide formation was linear, and (b) levels ofanti-diol-epoxide formed were highly dependent upon the starting BP concentration.anti-Diol-epoxide production increased at starting BP concentrations of 0–12 μmand decreased in incubations containing 12–25 μmBP. However, between 25 and 100 μmBP,anti-diol-epoxide formation was stable at a level representing 65% of the peak production which occurred at a starting BP concentration of 12 μm. BP oxidation was competitively inhibited by (−)-trans-BP-7,8-dihydrodiol and about five times less effectively by the (+)-trans-BP-7,8-dihydrodiol. The inability of a severalfold excess of BP (25–100 μm) to totally inhibit BP-7,8-dihydrodiol oxidation was explained by the presence of a microsomal substrate compartment which was saturated at only 6–8 μmBP, the remaining BP present as aggregates in the aqueous compartment. Purification of microsomes by Sepharose 2B gel filtration after reaction with [3H]BP also indicated that BP-7,8-dihydrodiol was preferentially concentrated in the microsome compartment leading to a net increase in the ratio of BP-7,8-dihydrodiol to BP in the microsomal compartment, which favored BP-7,8-dihydrodiol oxidation to yield the biologically activeanti-diol-epoxide.