Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 43, Issue 11, Pages 1607-1617Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2005.05.002
Keywords
heterocyclic amines; 2-nitrosoamino-3-methylimidazo[4,5-f]quinoline; nucleotide adducts; genotoxicity; colon cancer; inflammation
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Funding
- NCI NIH HHS [CA72613] Funding Source: Medline
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Heterocyclic amines and inflammation have been implicated in the etiology of colon cancer. We have recently demonstrated that during autoxidation of the inflammatory mediator nitric oxide 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) undergoes nitrosation to form 2-nitrosoamino-3-methylimidazo[4,5-f]quinoline (N-NO-IQ). This study evaluates the genotoxicity of N-NO-IQ and compares the adducts it forms to those of 2-hydroxyamino-3-methylimidazo[4,5-jlquinoline (N-OH-IQ). N-NO-IQ was incubated with 2'-deoxyguanosine 3'-monophosphate (dGp) under a variety of inflammatory conditions. P-32-Postlabeling demonstrated the presence of multiple adducts. Incubation of N-OH-IQ with dGp at pH 7.4, 5.5, or 2.0 resulted in the formation of a single major adduct, N-(deoxyguanosin-8-yl)-IQ (dG-C8-IQ). Using a combination of P-32-postlabeling, HPLC, and nuclease P 1 treatment, N-NO-IQ was shown to produce dG-C8-IQ under several different conditions. HOC] oxidation of N-NO-IQ increased dG-C8-IQ formation, and this was further increased as pH decreased from 7.4 to 5.5. Oxidation of N-NO-IQ formed a new adduct, adduct 2, while in the absence of oxidants adduct in was the major adduct. Adducts 2 and m were not formed by N-OH-IQ and not further identified. The results demonstrate that N-NO-IQ forms N-(deoxyguanosin-8-yl)-IQ, is genotoxic, is activated by conditions that mediate inflammatory responses, and is a possible cancer risk factor for individuals with colitis, inflammation of the colon. (c) 2005 Elsevier Ltd. All rights reserved.
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