Chang R L, Battista S, Wong C Q, Kumar S, Kole P L, Sikka H C, Balani S K, Jerina D M, Conney A H, Wood A W
Department of Chemical Biology and Pharmacognosy, College of Pharmacy, Rutgers, State University of New Jersey, Piscataway 08855.
Carcinogenesis. 1993 Nov;14(11):2233-7. doi: 10.1093/carcin/14.11.2233.
The mutagenic activities of the enantiomers of the diastereomeric pair of bay-region 10,11-diol-8,9-epoxides of dibenz[a,h]acridine (DB[a,h]ACR) were evaluated in histidine-dependent strains of Salmonella typhimurium and in cultured Chinese hamster V79 cells. In strains TA98 and TA100 of S.typhimurium, the (-)-[8S,9R,10R,11S] diol-epoxide was the most mutagenic compound, inducing 1200 and 6900 His+ revertants/nmol respectively. The mutagenic activity of each of the remaining three isomers was essentially independent of the bacterial strain used and had 14-72% of the activity of the [S,R,R,S] isomer. However, in Chinese hamster V79 cells, the (+)-[8R,9S,10S,11R] diol-epoxide was the most mutagenic compound (68 8-azaguanine resistant variants/nmol/10(5) cells), inducing from 2 to 11 times as many mutations as the other three isomers. These results are analogous to previous studies with the bay-region diol-epoxides of other polycyclic hydrocarbons in that the isomer with [R,S,S,R] absolute configuration has had variable activity in the bacterial assays, but has generally been the most active in the mammalian cells. Furthermore, this isomer has almost always been highly tumorigenic in the mouse.
在鼠伤寒沙门氏菌的组氨酸依赖型菌株和培养的中国仓鼠V79细胞中，评估了二苯并[a,h]吖啶（DB[a,h]ACR）的湾区10,11 - 二醇 - 8,9 - 环氧化物非对映异构体对映体的诱变活性。在鼠伤寒沙门氏菌的TA98和TA100菌株中，(-)-[8S,9R,10R,11S]二醇环氧化物是最具诱变活性的化合物，分别诱导出1200和6900个His+回复突变体/ nmol。其余三种异构体中每种的诱变活性基本上与所使用的细菌菌株无关，且具有[S,R,R,S]异构体活性的14 - 72%。然而，在中国仓鼠V79细胞中，(+)-[8R,9S,10S,11R]二醇环氧化物是最具诱变活性的化合物（68个8 - 氮杂鸟嘌呤抗性变体/ nmol / 10(5)个细胞），诱导的突变数是其他三种异构体的2至11倍。这些结果类似于先前对其他多环烃的湾区二醇环氧化物的研究，即具有[R,S,S,R]绝对构型的异构体在细菌试验中的活性各不相同，但在哺乳动物细胞中通常是最具活性的。此外，这种异构体在小鼠中几乎总是具有高度致瘤性。
