Measurement of the Heterocyclic Amines 2-Amino-9H-pyrido[2,3-b]indole and 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in Urine: Effects of Cigarette Smoking

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• 作者：Dmitri Konorev ; Joseph S. Koopmeiners ; Yijin Tang ; Elizabeth A. Franck Thompson ; Joni A. Jensen ; Dorothy K. Hatsukami ; Robert J. Turesky
• 刊名：Chemical Research in Toxicology
• 出版年：2015
• 出版时间：December 21, 2015
• 年：2015
• 卷：28
• 期：12
• 页码：2390-2399
• 全文大小：509K
• ISSN：1520-5010

文摘

2-Amino-9H-pyrido[2,3-b]indole (A伪C) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogenic heterocyclic aromatic amines (HAAs) formed during the combustion of tobacco and during the high-temperature cooking of meats. Human enzymes biotransform A伪C and PhIP into reactive metabolites, which can bind to DNA and lead to mutations. We sought to understand the relative contribution of smoking and diet to the exposure of A伪C and PhIP, by determining levels of A伪C, its ring-oxidized conjugate 2-amino-9H-pyrido[2,3-b]indole-3-yl sulfate (A伪C-3-OSO₃H), and PhIP in urine of smokers on a free-choice diet before and after a six week tobacco smoking cessation study. A伪C and A伪C-3-OSO₃H were detected in more than 90% of the urine samples of all subjects during the smoking phase. The geometric mean levels of urinary A伪C during the smoking and cessation phases were 24.3 pg/mg creatinine and 3.2 pg/mg creatinine, and the geometric mean levels of A伪C-3-OSO₃H were 47.3 pg/mg creatinine and 3.7 pg/mg creatinine. These decreases in the mean levels of A伪C and A伪C-3-OSO₃H were, respectively, 87% and 92%, after the cessation of tobacco (P < 0.0007). However, PhIP was detected in <10% of the urine samples, and the exposure to PhIP was not correlated to smoking. Epidemiological studies have reported that smoking is a risk factor for cancer of the liver and gastrointestinal tract. It is noteworthy that A伪C is a hepatocellular carcinogen and induces aberrant crypt foci, early biomarkers of colon cancer, in rodents. Our urinary biomarker data demonstrate that tobacco smoking is a significant source of A伪C exposure. Further studies are warranted to examine the potential role of A伪C as a risk factor for hepatocellular and gastrointestinal cancer in smokers.