title: 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.
abstract: 2-Amino-9H-pyrido[2,3-b]indole (AαC) 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 AαC 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 AαC and PhIP, by determining levels of AαC, its ring-oxidized conjugate 2-amino-9H-pyrido[2,3-b]indole-3-yl sulfate (AαC-3-OSO3H), and PhIP in urine of smokers on a free-choice diet before and after a six week tobacco smoking cessation study. AαC and AαC-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 AαC during the smoking and cessation phases were 24.3 pg/mg creatinine and 3.2 pg/mg creatinine, and the geometric mean levels of AαC-3-OSO3H were 47.3 pg/mg creatinine and 3.7 pg/mg creatinine. These decreases in the mean levels of AαC and AαC-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 AαC 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 AαC exposure. Further studies are warranted to examine the potential role of AαC as a risk factor for hepatocellular and gastrointestinal cancer in smokers.
authors.affiliation: Department of Medicinal Chemistry and Masonic Cancer Center, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Konorev
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Koopmeiners
authors.affiliation: Division of Environmental Health Sciences, Wadsworth Center, New York State Department of Health , Albany, New York 12201, United States.
authors.forename: Yijin
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Tobacco Use Programs, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Franck Thompson
authors.affiliation: Tobacco Use Programs, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Joni A
authors.initials: JA
authors.lastname: Jensen
authors.affiliation: Tobacco Use Programs, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Dorothy K
authors.initials: DK
authors.lastname: Hatsukami
authors.affiliation: Department of Medicinal Chemistry and Masonic Cancer Center, University of Minnesota , Minneapolis, Minnesota 55455, United States.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Turesky
mesh_terms: D024322:Amino Acids, Aromatic / Q000737:chemistry* / Q000652:urine*; D000631:Aminopyridines / Q000737:chemistry* / Q000652:urine; D002853:Chromatography, Liquid; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000652:urine*; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000652:urine; D057230:Limit of Detection; D013058:Mass Spectrometry; D015394:Molecular Structure; D012907:Smoking; D016540:Smoking Cessation
chemical_list: C000609566:2-amino-3-hydroxy-9H-pyrido(2,3-b)indole; D024322:Amino Acids, Aromatic; D000631:Aminopyridines; D006571:Heterocyclic Compounds; D007211:Indoles