MacLeod M C, Selkirk J K
Carcinogenesis. 1982;3(3):287-92. doi: 10.1093/carcin/3.3.287.
The physical interactions of two diol-epoxides derived from benzo [a] pyrene (B[a]P), 7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydro B[a]P (BPDE) and 9,10-dihydroxy-7,8-oxy-7,8,9,10-tetrahydro B[a]P, (reverse BPDE) with DNA have been studied in a simple, in vitro system. The effects of DNA on the rates of hydrolysis of BPDE and reverse BPDE were studied by fluorescence spectroscopy. For both compounds, interaction with DNA was indicated by an increase in the rate of hydrolysis in the presence of DNA. This increased hydrolysis was more marked for BPDE than for reverse BPDE. Direct confirmation of physical binding was obtained by u.v. spectroscopy, where a 10 nm redshift in absorbance maxima characteristic of polycyclic aromatic hydrocarbon.DNA intercalation complexes was observed. Using absorbance changes to monitor binding, association constants of 6580 L/mol and 5080 L/mol were determined for BPDE and reverse BPDE, respectively. Consistent with the intercalation model, binding was inhibited by low concentrations of Mg2+. The enhancement of hydrolytic rate by DNA for BPDE and reverse BPDE was also inhibited by low concentrations of Mg2+, suggesting involvement of intercalation complexes in the mechanism of enhanced hydrolysis.
在一个简单的体外系统中，研究了源自苯并[a]芘（B[a]P）的两种二醇环氧化物，即7,8 - 二羟基 - 9,10 - 环氧 - 7,8,9,10 - 四氢苯并[a]芘（BPDE）和9,10 - 二羟基 - 7,8 - 环氧 - 7,8,9,10 - 四氢苯并[a]芘（反式BPDE）与DNA的物理相互作用。通过荧光光谱研究了DNA对BPDE和反式BPDE水解速率的影响。对于这两种化合物，在DNA存在下，水解速率增加表明它们与DNA发生了相互作用。这种水解增加在BPDE中比在反式BPDE中更明显。通过紫外光谱直接证实了物理结合，观察到多环芳烃 - DNA嵌入复合物特征性的最大吸收峰发生了10 nm的红移。利用吸光度变化监测结合，分别测定了BPDE和反式BPDE的缔合常数为6580 L/mol和5080 L/mol。与嵌入模型一致，低浓度的Mg2 +抑制了结合。低浓度的Mg2 +也抑制了DNA对BPDE和反式BPDE水解速率的增强作用，表明嵌入复合物参与了水解增强机制。
