Kim M H, Geacintov N E, Pope M, Pataki J, Harvey R G
Carcinogenesis. 1985 Jan;6(1):121-6. doi: 10.1093/carcin/6.1.121.
Reactions of trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (anti-5-MeCDE) with DNA and the effects of ionic strength on the reaction were studied in aqueous buffer solution (5 mM sodium phosphate, pH 7) by means of absorption and fluorescence spectroscopy. The results are compared with those obtained with the widely studied metabolite model compound trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BaPDE). The rate constant of hydrolysis of 5-MeCDE is k = 1.0 X 10(4)/S, which is approximately 35 times smaller than the value of k for BaPDE under similar conditions. As in the case of BaPDE, the rate of reaction of 5-MeCDE is accelerated in the presence of DNA. This effect is attributed to the rapid formation of physical association complexes (binding constant K) and the subsequent slower formation (rate constant k3) of carbocations at DNA binding sites, which in turn decay rapidly via hydrolysis to tetraols (1,2,3,4-tetrahydroxytetrahydro-5-methylchrysene, 5-MeCT) and to covalent adducts. The values of K and k3 are 2800 +/- 300/M and 8.7 X 10(-3)/S respectively, and are reduced to 450 +/- 100/M and 1.8 X 10(-3)/S in the presence of 0.1 M NaCl. The fraction of 5-MeCDE molecules which bind covalently to DNA is, on the other hand, constant under these conditions and lies in the range of 5-8%. Similar values for the covalent binding are observed for BaPDE, even though the physical association constant K is approximately 10 times larger than for 5-MeCDE under similar conditions. This difference in the values of K are attributed to the larger aromatic ring system in BaPDE which allows for a higher interaction of this molecule with the bases of DNA. Finally, the tetraol derived from the hydrolysis of 5-MeCDE also binds non-covalently to DNA, but the value of K is approximately 3 times smaller than for the diol epoxide.
通过吸收光谱和荧光光谱法，在水缓冲溶液（5 mM磷酸钠，pH 7）中研究了反式-1,2-二羟基-反式-3,4-环氧-1,2,3,4-四氢-5-甲基屈（反式-5-MeCDE）与DNA的反应以及离子强度对该反应的影响。将结果与广泛研究的代谢物模型化合物反式-7,8-二羟基-反式-9,10-环氧-7,8,9,10-四氢苯并[a]芘（BaPDE）所获得的结果进行比较。5-MeCDE的水解速率常数为k = 1.0×10⁻⁴/s，在类似条件下，该值比BaPDE的k值小约35倍。与BaPDE的情况一样，在DNA存在下5-MeCDE的反应速率会加快。这种效应归因于物理缔合复合物（结合常数K）的快速形成以及随后在DNA结合位点处碳正离子的较慢形成（速率常数k₃），而碳正离子又通过水解迅速分解为四醇（1,2,3,4-四羟基四氢-5-甲基屈，5-MeCT）和共价加合物。K和k₃的值分别为2800±300/M和8.7×10⁻³/s，在0.1 M NaCl存在下分别降至450±100/M和1.8×10⁻³/s。另一方面，与DNA共价结合的5-MeCDE分子的比例在这些条件下是恒定的，范围在5％至8％之间。对于BaPDE，观察到共价结合的类似值，尽管在类似条件下物理缔合常数K比5-MeCDE大约10倍。K值的这种差异归因于BaPDE中较大的芳香环系统，这使得该分子与DNA碱基之间具有更高的相互作用。最后，由5-MeCDE水解产生的四醇也与DNA非共价结合，但其K值比二醇环氧化物小约3倍。
