Regan J D, Francis A A, Dunn W C, Hernandez O, Yagi H, Jerina D M
Chem Biol Interact. 1978 Mar;20(3):279-87. doi: 10.1016/0009-2797(78)90106-0.
The repair of human DNA after damage by known and potential metabolites of benzo(a)pyrene has been examined utilizing the bromodeoxyuridine photolysis assay. Repair was characterized as either ultraviolet ("long") or ionizing radiation type ("short") repair utilizing normal cells and cells deficient in ultraviolet-type repair endonuclease from a patient with xeroderma pigmentosum (XP). We have found that only (+/-)-7beta,8alpha-dihydroxy-9beta,-10beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BP diol epoxide 1) and its disastereomer, (+/-)-7beta,8alpha,-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BP diol epoxide 2) elicit damage to DNA which is recognizable by the ultraviolet excision repair system in normal human cells. Benzo(a)pyrene 4,5-, 9,10-, 11,12-oxides do not elicit damage which is repairable by this repair system. The 1,2-diol-3,4-epoxides from naphthalene have no measurable activity in our assay. These results indicate that both the benzo(a)pyrene ring structure and the diol epoxide groups are important in causing the damage to DNA which is repairable by the ultraviolet excision repair system. These results parallel the reported high mutagenic activity of these compounds and support the concept that benzo(a)pyrene 7,8-diol-9,10-epoxides may be the ultimate, metabolically activated forms of benzo(a)pyrene.
利用溴脱氧尿苷光解测定法，研究了苯并(a)芘已知的和潜在的代谢产物对人类DNA损伤后的修复情况。利用正常细胞和一名色素沉着干皮病（XP）患者体内缺乏紫外线型修复内切酶的细胞，将修复特征化为紫外线（“长”）或电离辐射型（“短”）修复。我们发现，只有(±)-7β,8α-二羟基-9β,-10β-环氧-7,8,9,10-四氢苯并(a)芘（BP二醇环氧化物1）及其非对映异构体(±)-7β,8α,-二羟基-9α,10α-环氧-7,8,9,10-四氢苯并(a)芘（BP二醇环氧化物2）会引发DNA损伤，而这种损伤在正常人类细胞中可被紫外线切除修复系统识别。苯并(a)芘4,5-、9,10-、11,12-氧化物不会引发可被该修复系统修复的损伤。萘的1,2-二醇-3,4-环氧化物在我们的测定中没有可测量的活性。这些结果表明，苯并(a)芘的环结构和二醇环氧化物基团在导致可被紫外线切除修复系统修复的DNA损伤方面都很重要。这些结果与报道的这些化合物的高诱变活性一致，并支持苯并(a)芘7,8-二醇-9,10-环氧化物可能是苯并(a)芘最终的、经代谢活化形式的概念。
