Geacintov N E, Cosman M, Mao B, Alfano A, Ibanez V, Harvey R G
Chemistry Department, New York University, NY 10003.
Carcinogenesis. 1991 Nov;12(11):2099-108. doi: 10.1093/carcin/12.11.2099.
The highly tumorigenic isomer (+)-7,8-dihydroxy-anti-9, 10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE] and its non-tumorigenic enantiomer (-)-anti-BPDE are known to react predominantly with the exocyclic amino group (N2) of deoxyguanine in DNA and to form adducts of different conformations. The spectroscopic characteristics (UV absorbance, fluorescence and circular dichroism) of stereochemically defined (+)-trans, (-)-trans, (+)-cis and (-)-cis d(5'-CACATGBPDETACAC) adducts in the single-stranded form, or complexed with the complementary strand d(5'-GTGTACATGTG) in aqueous solution, were investigated. The spectroscopic characteristics of the double-stranded d(5'-CACATGBPDETACAC).d(5'-GTGTACATGTG) adducts can be interpreted in terms of two types of conformations. In site I-type conformations, there is an approximately 10 nm red shift in the absorption maxima, which is attributed to significant pyrenyl residue-base interactions; in site II-type adducts, the red shift is only approximately 2-3 nm, and the pyrene ring system is located at external, solvent-exposed binding sites. The spectroscopic characteristics of the BPDE-modified duplexes are of the site II type for the (+)- and (-)-trans, and of the site I type for the (+)- and (-)-cis adducts. In adducts derived from the binding of (+)-anti-BPDE to poly(dG-dC).(dG-dC) and poly(dG).(dC), the trans/cis BPDE-N2-dG adduct ratio is 6 +/- 1; in the case of (-)-anti-BPDE this ratio is only 0.4 +/- 0.1 and 0.6 +/- 0.15 in poly(dG-dC).(dG-dC) and poly(dG).(dC) respectively. The spectroscopic properties of these BPDE-modified polynucleotide adducts are consistent with those of the BPDE-modified oligonucleotide complexes; the cis adducts are correlated with site I adduct conformations, while the trans adducts are of the site II type. The correlations between adduct characteristics and biological activities of the two BPDE enantiomers are discussed.
高致瘤性异构体（+）-7,8-二羟基-反式-9,10-环氧-7,8,9,10-四氢苯并[a]芘[（+）-反式-BPDE]及其非致瘤性对映体（-）-反式-BPDE已知主要与DNA中脱氧鸟苷的外环氨基（N2）反应，并形成不同构象的加合物。研究了单链形式或在水溶液中与互补链d（5'-GTGTACATGTG）复合的立体化学定义的（+）-反式、（-）-反式、（+）-顺式和（-）-顺式d（5'-CACATGBPDETACAC）加合物的光谱特征（紫外吸收、荧光和圆二色性）。双链d（5'-CACATGBPDETACAC）.d（5'-GTGTACATGTG）加合物的光谱特征可以用两种构象类型来解释。在位点I型构象中，吸收最大值有大约10nm的红移，这归因于显著的芘基残基-碱基相互作用；在位点II型加合物中，红移仅约2-3nm，芘环系统位于外部、溶剂暴露的结合位点。（+）-和（-）-反式BPDE修饰的双链体的光谱特征属于位点II型，而（+）-和（-）-顺式加合物的光谱特征属于位点I型。在（+）-反式-BPDE与聚（dG-dC）.（dG-dC）和聚（dG）.（dC）结合产生的加合物中，反式/顺式BPDE-N2-dG加合物比率为6±1；对于（-）-反式-BPDE，在聚（dG-dC）.（dG-dC）和聚（dG）.（dC）中该比率分别仅为0.4±0.1和0.6±0.15。这些BPDE修饰的多核苷酸加合物的光谱性质与BPDE修饰的寡核苷酸复合物的光谱性质一致；顺式加合物与位点I加合物构象相关，而反式加合物属于位点II型。讨论了两种BPDE对映体的加合物特征与生物活性之间的相关性。
