title: DNA adduct formation of 2-amino-9H-pyrido[2,3-b]indole and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline in mouse liver and extrahepatic tissues during a subchronic feeding study.
abstract: Tobacco smoking is a risk factor for cancers of the liver and gastrointestinal (GI) tract, but the causal agents responsible for these cancers are uncertain. 2-Amino-9H-pyrido[2,3-b]indole (AαC) is an abundant heterocyclic aromatic amine present in tobacco smoke. AαC is a liver carcinogen and both a transgene mutagen and inducer of aberrant crypt foci in the colon of mice. We hypothesize that AαC may contribute to DNA damage and tumorigenesis in these organs of smokers. The potential of AαC to induce DNA adduct formation in liver, organs of the GI tract, lung, and urinary bladder, which are target organs of cancer in smokers, was examined using the C57BL/6 mouse as an animal model. AαC (400 or 800 ppm) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) (300 ppm), a liver and colon carcinogen in C57BL/6 mice, were given in the diet for up to 12 weeks. Liquid chromatography/mass spectrometry was employed to measure DNA adducts. The major DNA adducts of both carcinogens were identified as deoxyguanosine-C8 adducts. The levels of formation of AαC- and MeIQ-DNA adducts were similar in liver and extrahepatic tissues when adjusted for dose. The highest levels of adducts occurred in liver, followed by urinary bladder, and then in cecum and colon; lower DNA adduct levels were formed in the lung and pancreas following 12 weeks of feeding. The high levels of AαC adduct formed in liver, GI tract, and bladder of C57BL/6 mice reinforce the notion that AαC may contribute to DNA damage and cancer of these organs in smokers.
authors.affiliation: Division of Environmental Health Sciences, Wadsworth Center, New York State Department of Health, Albany, New York 12201, USA.
authors.forename: Yijin
authors.initials: Y
authors.lastname: Tang
authors.forename: Fekadu
authors.initials: F
authors.lastname: Kassie
authors.forename: Xuemin
authors.initials: X
authors.lastname: Qian
authors.forename: Buzayew
authors.initials: B
authors.lastname: Ansha
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Turesky
mesh_terms: D000818:Animals; D002243:Carbolines / Q000378:metabolism / Q000633:toxicity*; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011804:Quinolines / Q000378:metabolism / Q000633:toxicity*; D018675:Toxicity Tests; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002243:Carbolines; D002273:Carcinogens; D018736:DNA Adducts; D011804:Quinolines; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline; C017822:2-amino-9H-pyrido(2,3-b)indole
keywords: DNA adducts; carcinogens; heterocyclic aromatic amines.; tobacco smoke
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