Osborne M R
Institute of Cancer Research, Chester Beatty Laboratory, London, U.K.
Chem Biol Interact. 1990;75(2):131-40. doi: 10.1016/0009-2797(90)90113-2.
Benzopyrene diol epoxide (BPDE; (+)-7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene), the ultimate carcinogen derived from the polycyclic hydrocarbon benzo[a]pyrene, reacts principally with the guanine bases in DNA. Nineteen double stranded, self-complementary oligonucleotides, containing deoxyguanosine in various sequence contexts, were each treated with tritium labelled BPDE. The extent of reaction was determined by releasing the BPDE-guanine adduct with acid, isolating it by chromatography on a reverse-phase column, and estimating it by its radioactivity. Oligonucleotides containing an isolated guanine, such as AAGTACTT, were little affected by BPDE. Reactivity was increased where the guanine was flanked by another guanine on the same strand (e.g. TACCTAGGTA) or on the complementary strand (e.g. TATTCGAATA), and was highest in mixed G-C sequences such as ATCCGGAT. The results should help predict major sites of attack of BPDE on cellular proto-oncogenes.
苯并芘二醇环氧化物（BPDE；(+)-7R,8S-二羟基-9S,10R-环氧-7,8,9,10-四氢苯并[a]芘）是多环烃苯并[a]芘衍生的最终致癌物，主要与DNA中的鸟嘌呤碱基发生反应。19种双链、自我互补的寡核苷酸，在不同序列背景下含有脱氧鸟苷，每种都用氚标记的BPDE处理。通过用酸释放BPDE-鸟嘌呤加合物、在反相柱上进行色谱分离并通过其放射性进行估算来确定反应程度。含有孤立鸟嘌呤的寡核苷酸，如AAGTACTT，受BPDE的影响很小。当鸟嘌呤在同一条链上（如TACCTAGGTA）或互补链上（如TATTCGAATA）被另一个鸟嘌呤侧翼时，反应性增加，在混合的G-C序列如ATCCGGAT中反应性最高。这些结果应有助于预测BPDE对细胞原癌基因的主要攻击位点。
