2-Amino-9H-pyrido[2,3-b]indole: A Potential Colorectal Carcinogen Formed in Tobacco

Principal Investigator: Robert Turesky

Funding Mechanism: National Institutes of Health- Grant

ID number: 3 R01 CA134700-03S1

Award Date: 9/17/2012

Institution: Wadsworth Center

Although smoking is a known risk factor for cancers of the gastrointestinal (GI) tract, little is known about the tobacco constituents that are potentially responsible for GI cancer development. Investigators previously reported that the heterocyclic aromatic amine 2-amino-9H-pyrido[2,3-b]indole (AαC) -- the most abundant aromatic amine carcinogen formed in tobacco smoke and a rodent GI genotoxicant -- is present in the urine of tobacco smokers in a dose-dependent manner but is absent in the urine of nonsmokers. The parent grant characterized the metabolic pathways involved in AαC bioactivation and detoxication in order to elucidate the causal role of AαC exposure in smoking-related GI cancers in humans. The objective of this study is to examine the reaction products of the carcinogenic metabolites of AαC with serum albumin and hemoglobin in order to eventually develop biomarkers of AαC adducts of these blood proteins as potential human biomarkers. Specific aims are: (1) to examine the reaction products of the carcinogenic metabolites of AαC with serum albumin and hemoglobin, in order to establish AαC adducts of these blood proteins as biomarkers; and (2) to develop analytical mass spectrometry methods to measure AαC blood protein biomarkers. Investigators will develop biomarkers based on blood samples obtained from seven habitual smokers and three nonsmokers. This investigation will establish a set of AαC biomarkers that can be used in population-based cohort studies of smoking and GI cancer and in analyses that measure and compare tobacco products’ toxicity and carcinogenicity.