Szeliga J, Amin S, Zhang F J, Harvey R G
Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA.
Chem Res Toxicol. 1999 Apr;12(4):347-52. doi: 10.1021/tx980228o.
Both syn and anti dihydrodiol epoxides from 5-methylchrysene (5-MCDE) and 5,6-dimethylchrysene (5,6-DMCDE) were reacted under the same conditions with native DNA, denatured DNA, and purine deoxyribonucleotides, and the products were quantified. The extents of reaction with the deoxyribonucleotides were consistently greater for 5,6-DMCDE than for 5-MCDE. The yield of adducts in the reaction with DNA ranged from being a few-fold to 50-fold greater than those found in the corresponding deoxyribonucleotide reactions for both 5-MCDE and 5,6-DMCDE. The DNA-dependent enhancement of product yield was greater for 5-MCDE than for 5,6-DMCDE with a few exceptions among cis and trans deoxyadenosine adducts. The most substantial differences in DNA-dependent enhancement were found for deoxyguanosine adducts; thus, steric hindrance between the 6-methyl group in the 5,6-DMCDE and the minor groove in the DNA double helix may account for the greater DNA-dependent enhancement found in the 5-MCDE reactions.
来自5-甲基屈（5-MCDE）和5,6-二甲基屈（5,6-DMCDE）的顺式和反式二氢二醇环氧化物在相同条件下与天然DNA、变性DNA和嘌呤脱氧核糖核苷酸反应，并对产物进行定量。5,6-DMCDE与脱氧核糖核苷酸的反应程度始终高于5-MCDE。对于5-MCDE和5,6-DMCDE，与DNA反应的加合物产率比相应脱氧核糖核苷酸反应中的产率高几倍至50倍。除了顺式和反式脱氧腺苷加合物中的少数例外情况，5-MCDE的DNA依赖性产物产率增强比5,6-DMCDE更大。在脱氧鸟苷加合物中发现了DNA依赖性增强的最显著差异；因此，5,6-DMCDE中6-甲基与DNA双螺旋小沟之间的空间位阻可能解释了在5-MCDE反应中发现的更大的DNA依赖性增强。
