Hall M, Parker D K, Hewer A J, Phillips D H, Grover P L
Chester Beatty Laboratories, Institute of Cancer Research, London, UK.
Carcinogenesis. 1988 May;9(5):865-8. doi: 10.1093/carcin/9.5.865.
Incubation of r-1,t-2-dihydroxy-t-3,4-oxy-1,2,3,4-tetrahydrochrysene (anti-chrysene-1,2-diol 3,4-oxide), the bay-region diol-epoxide of chrysene, with rat liver microsomes in the presence of NADP+ and DNA, followed by 32P-postlabelling analysis of the DNA, revealed the presence of at least two adducts not detected when anti-chrysene-1,2-diol 3,4-oxide was incubated with DNA alone. The formation of these adducts was not blocked by the epoxide hydrolase inhibitor 1,1,1-trichloropropane-2,3-oxide. One of the adducts cochromatographed with the adduct spot obtained when authentic 9-hydroxy-r-1,t-2-dihydroxy-t-3,4-oxy-1,2,3,4-tetrahydrochrysene (anti-9-OH-chrysene-1,2-diol 3,4-oxide) was reacted with DNA. Evidence suggested that a second adduct could also be formed by further metabolism of anti-9-OH-chrysene-1,2-diol 3,4-oxide. In addition, evidence was obtained for the further metabolism of the syn-isomer of chrysene 1,2-diol 3,4-oxide and the anti-isomer of a non-bay-region diol-epoxide of dibenz[a,c]anthracene to DNA binding species, but not for that of either the anti- or syn-isomers of the bay-region diol-epoxide of benzo[a]pyrene, the anti-isomers of the bay-region or a non-bay-region diol-epoxide of benz[a]anthracene, or the anti-isomer of the bay-region diol-epoxide of benzo[b]fluoranthene.
将1,2,3,4 - 四氢屈的湾区二醇环氧化物r-1,t-2-二羟基-t-3,4-氧代-1,2,3,4-四氢屈（反式屈-1,2-二醇3,4-氧化物）与大鼠肝微粒体在NADP+和DNA存在的条件下温育，随后对DNA进行32P后标记分析，结果显示存在至少两种单独将反式屈-1,2-二醇3,4-氧化物与DNA温育时未检测到的加合物。这些加合物的形成未被环氧化物水解酶抑制剂1,1,1-三氯丙烷-2,3-氧化物阻断。其中一种加合物与真实的9-羟基-r-1,t-2-二羟基-t-3,4-氧代-1,2,3,4-四氢屈（反式-9-OH-屈-1,2-二醇3,4-氧化物）与DNA反应时得到的加合物斑点共色谱。有证据表明，第二种加合物也可能由反式-9-OH-屈-1,2-二醇3,4-氧化物的进一步代谢形成。此外，还获得了证据表明屈1,2-二醇3,4-氧化物的顺式异构体和二苯并[a,c]蒽的非湾区二醇环氧化物的反式异构体可进一步代谢为与DNA结合的物种，但苯并[a]芘的湾区二醇环氧化物的反式或顺式异构体、苯并[a]蒽的湾区或非湾区二醇环氧化物的反式异构体以及苯并[b]荧蒽的湾区二醇环氧化物的反式异构体则不然。
