Rapid release of carcinogen-guanine adducts from DNA after reaction with N-acetoxy-2-acetylaminofluorene or N-benzoyloxy-N-methyl-4-aminoazobenzene.
Rapid release of carcinogen-guanine adducts from DNA after reaction with N-acetoxy-2-acetylaminofluorene or N-benzoyloxy-N-methyl-4-aminoazobenzene.
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与 N-乙酰氧基-2-乙酰氨基芴或 N-苯甲酰氧基-N-甲基-4-氨基偶氮苯反应后，致癌物-鸟嘌呤加合物从 DNA 中快速释放。
DOI：
10.1093/carcin/3.1.81
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发表时间：
1982
期刊：
影响因子：
4.7
通讯作者：
Miller,EC
中科院分区：
文献类型：
--
作者：
Tarpley,WG;Miller,JA;Miller,EC
N-苯甲酰氧基-N-甲基-4-氨基偶氮苯（N-benzoyloxy-MAB）或N-乙酰氧基-N-乙酰基-2-氨基芴（N-acetoxy-AAF），模型最终芳香胺或酰胺致癌物，与[嘌呤-14 C]DNA在pH7.4或N-羟基-2-氨基芴（N-hydroxy-AF）在pH4.6反应，导致快速释放不与DNA沉淀的含14 C产物。与N-乙酰氧基-AAF反应得到四种这样的产物，与N-羟基-AF反应得到两种，与N-苯甲酰氧基-MAB反应得到六种。根据所用的DNA样品，来自与N-苯甲酰氧基-MAB或N-乙酰氧基-AAF反应的这些产物中14 C的总量为来自相同反应混合物的DNA中N-（脱氧鸟苷-8-基）-MAB或N-（脱氧鸟苷-8-基）-AAF残基的量的约5%至多达30-40%。与N-乙酰氧基-[乙酰基-3H]AAF的反应表明，两种主要产物保留了来自N-乙酰氧基-AAF的酰胺残基。当用[鸟嘌呤-（8- 3 H; 8- 14 C）;腺嘌呤-（2，8 - 3 H; 8- 14 C）]DNA进行反应时，由N-乙酰氧基-AAF形成的两种主要产物和由N-苯甲酰氧基-MAB形成的四种产物具有非常低的3 H：14 C比率;这些比率是失去8- 3 H的鸟嘌呤衍生物的预期比率。对主要的DNA加合物N-（脱氧鸟苷-8-基）-MAB和N-（脱氧鸟苷-8-基）-AAF的研究表明，这些核苷没有形成新的加合物。这些数据表明，两个主要的AAF产品和四个MAB加合物的研究是鸟嘌呤衍生物的N-7取代的加合物的DNA脱嘌呤形成的。
Reaction of N-benzoyloxy-N-methyl-4-aminoazobenzene (N-benzoyloxy-MAB) or N-acetoxy-N-acetyl-2-aminofluorene (N-acetoxy-AAF), model ultimate aromatic amine or amide carcinogens, with [purine-14C]DNA at pH 7.4 or reaction of N-hydroxy-2-aminofluorene (N-hydroxy-AF) at pH 4.6 resulted in the rapid release of14C-containing products not precipitable with the DNA. Four such products were obtained on reaction with N-acetoxy-AAF, two with N-hydroxy-AF, and six with N-benzoyloxy-MAB. Depending on the DNA sample used, the total amounts of14C in these products from the reactions with N-benzoyloxy-MAB or N-acetoxy-AAF ranged from about 5% to as much as 30–40% of the amounts in the N-(deoxyguanosin-8-yl)-MAB or N-(deoxyguanosin-8-yl)-AAF residues in the DNA from the same reaction mixtures. Reactions with N-acetoxy-[acetyl-3H]AAF showed that the two major products retained the amide residue from the N-acetoxy-AAF. When the reactions were carried out with [guanine-(8-3H; 8-14C); adenine-(2,8-3H; 8-14C)]DNA, the two major products formed from N-acetoxy-AAF and four products formed from N-benzoyloxy-MAB had very low3H:14C ratios; these ratios were those expected for guanine derivatives which had lost the 8-3H. Studies on the major DNA adducts N-(deoxyguanosin-8-yl)-MAB and N-(deoxyguanosin-8-yl)-AAF indicated that the new adducts were not formed from these nucleosides. The data suggest that the two major AAF products and the four MAB adducts studied are guanine derivatives formed by depurination of N-7 substituted adducts in the DNA.