School of Pharmacy at MCV Campus, Virginia Commonwealth University, Smith Building, Room 356C, Richmond, VA 23298-0533, USA.
Environ Toxicol Pharmacol. 2002 Jan;11(1):23-6. doi: 10.1016/s1382-6689(01)00098-9.
One of the carcinogens from cigarette smoke, 4-aminobiphenyl, is excreted in urine as 4-N-hydroxyl aminobiphenyl metabolite conjugates that undergo pH mediated activation to nitreneum ions leading to bladder tumorigenesis via DNA adduct formation. We hypothesize that changing the pH of smokers' urine might impact the mutagenic outcome. 4-NOHABP was synthesized (∼98% purity), structure confirmed by TLC and NMR; mutagenic activity, assessed by the Ames test, was measured after pre-incubation in buffer solutions or human urine at pH 4, 6, 7 and 8. An inverse correlation was observed between number of histidine revertant colonies and pH (r(2)=0.89), 4-NOHABP exhibiting significant mutagenicity at pH 4.0 (P<0.05).
香烟烟雾中的一种致癌物质 4-氨基联苯，以 4-N-羟基氨基联苯代谢物轭合物的形式从尿液中排出，这些轭合物在 pH 介导下发生激活，形成氮烯离子，导致膀胱肿瘤形成，通过 DNA 加合物的形成。我们假设改变吸烟者尿液的 pH 值可能会影响致突变的结果。合成了 4-NOHABP（纯度约为 98%），通过薄层色谱和 NMR 确认其结构；通过 Ames 试验评估其诱变活性，在 pH 值为 4、6、7 和 8 的缓冲液或人尿中进行预孵育后进行测量。观察到组氨酸回复菌落数与 pH 值之间呈负相关（r(2)=0.89），4-NOHABP 在 pH 值为 4.0 时表现出显著的致突变性（P<0.05）。
