MacLeod M C, Zachary K
Chem Biol Interact. 1985 Jun;54(1):45-55. doi: 10.1016/s0009-2797(85)80151-4.
The interactions of the (+)- and (-)-enantiomers of 7r,8t-dihydroxy-9t,10t-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE-I) with purified DNA have been studied in vitro. These compounds are formed by cellular metabolism of the potent environmental carcinogen benzo[a]pyrene, and the (+)-enantiomer is thought to be the ultimate carcinogenic metabolite. Non-covalent, intercalative binding was measured spectrophotometrically, hydrolysis was measured spectrofluorometrically and covalent binding was detected by liquid scintillation counting. No significant differences were found in the association constants for intercalative binding or in the ability of DNA to catalyse the hydrolysis of the two enantiomers. Covalent DNA binding was 4.5-fold higher for the (+)-enantiomer. When DNA was pretreated with a molar equivalent of the (-)-enantiomer, its subsequent ability to enhance the rate of BPDE-I hydrolysis and to bind covalently to (+)-BPDE-I was unimpaired. This suggests that the participation of the DNA in the hydrolysis reaction does not alter the DNA and therefore that the rate-enhancement is true catalysis.
已在体外研究了7r,8t - 二羟基 - 9t,10t - 氧 - 7,8,9,10 - 四氢苯并[a]芘（BPDE - I）的（+） - 和（ - ） - 对映体与纯化DNA的相互作用。这些化合物由强效环境致癌物苯并[a]芘的细胞代谢形成，并且（+） - 对映体被认为是最终致癌代谢物。通过分光光度法测量非共价插入结合，通过荧光分光光度法测量水解，并通过液体闪烁计数检测共价结合。在插入结合的缔合常数或DNA催化两种对映体水解的能力方面未发现显著差异。（+） - 对映体的共价DNA结合高出4.5倍。当用摩尔当量的（ - ） - 对映体预处理DNA时，其随后增强BPDE - I水解速率并与（+） - BPDE - I共价结合的能力未受损。这表明DNA参与水解反应不会改变DNA，因此速率增强是真正的催化作用。
