2-Nitrosoamino-3-methylimidazo[4,5-f]quinoline activated by the inflammatory response forms nucleotide adducts

Lakshmi, Vijaya M.; Schut, Herman A.J.; Zenser, Terry V.

doi:10.1016/j.fct.2005.05.002

Cited by 11 publications

(13 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Wiese et al [47] have shown that hCOX enzymes have the ability to activate several environmental and dietary carcinogens, including MeIQx, 4-ABP and B[a]P. Alternative mechanisms of metabolism of heterocyclic amines such as IQ and MeIQx yield similar types of adducts as their N-OH analogues. Both N-NO-IQ and N-OH-IQ formed dG-C8-IQ, and comigration of these adducts was confirmed by 32 P-postlabeling and HPLC methods [48]. The N-Nitroso analogues of IQ and MeIQx, activated by conditions that mediate inflammatory responses therefore have the ability to bind to DNA and form dG-C8 adducts, and have genotoxic potential [48,49].…”

Section: Discussionmentioning

confidence: 93%

“…Both N-NO-IQ and N-OH-IQ formed dG-C8-IQ, and comigration of these adducts was confirmed by 32 P-postlabeling and HPLC methods [48]. The N-Nitroso analogues of IQ and MeIQx, activated by conditions that mediate inflammatory responses therefore have the ability to bind to DNA and form dG-C8 adducts, and have genotoxic potential [48,49]. Formation of DMABP-derived adducts by pathways other than N-hydroxylation could partly explain the dose-dependent reduction of these adduct levels by celecoxib.…”

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

Dose-dependent reduction of 3,2′-dimethyl-4-aminobiphenyl-derived DNA adducts in colon and liver of rats administered celecoxib

Ravoori

Feng

Neale

et al. 2008

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

View full text Add to dashboard Cite

Colon cancer is second leading cause of cancer-related deaths in Western countries. Diet and smoking, which contain aromatic and heterocyclic amines, are major risk factors for colon cancer. Colorectal cancers have a natural history of long latency and therefore provide ample opportunities for effective chemoprevention. 3,2'-Dimethyl-4-aminobiphenyl (DMABP) is an experimental aromatic amine that causes cancer in rat colon and serves as an experimental model for arylamine and heterocyclic amine mutagens derived from diet and smoking. In this study, we investigated the effects of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor on DMABP-induced DNA adduct formation in rat liver and colon. Male F-344 rats (5-weeks old) were provided free access to modified AIN-76A rat chow containing 0 (control), 500, 1000, or 1500 ppm celecoxib. Two weeks later, the rats received a subcutaneous injection of 100 mg/kg DMABP in peanut oil. Two days after DMABP treatment, the rats were killed and DMABP-derived adducts were analyzed in colon and liver DNA by butanol extraction-mediated 32 P-postlabeling. Two major DNA adducts, identified as dG-C8-DMABP and dG-N 2 -DMABP, were detected in liver and colon of rats treated with DMABP. These DNA adducts were diminished approximately 35-40% with 500 ppm and 65-70% with 1,000 ppm celecoxib. In the colon, no further decline in DNA adducts was observed at 1500 ppm. The same DMABP-DNA adducts also were detected in the liver and were also diminished by celecoxib treatment. The reduction in DMABP-DNA adduct levels in celecoxib-treated animals provides further support for celecoxib as a chemopreventive agent for colorectal cancer.

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 95%

Dose-dependent reduction of 3,2′-dimethyl-4-aminobiphenyl-derived DNA adducts in colon and liver of rats administered celecoxib

Ravoori

Feng

Neale

et al. 2008

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

View full text Add to dashboard Cite

show abstract

“…Both N-OH-IQ and N-OH-MeIQx have been shown to form C-8 deoxyguanosine adducts and these adducts are present in vivo [47, 48, 52]. A previous study has demonstrated N-NO-IQ formation of the same adduct as N-OH-IQ, N-(3′ monophosphodeoxy-guanosin-8-yl)-IQ [31]. This observation was reproduced in our study and extended to N-NO-MeIQx.…”

Section: Discussionmentioning

confidence: 99%

“…Samples were then scraped from the plates and treated with nuclease P1 (0.2 mg/ml), which catalyzes hydrolysis of the 3′-phosphate group of the d( 32 P)pGp adduct to give the d( 32 P)pG adduct. Samples were analyzed by HPLC, with eluent radioactivity measured using a FLO-ONE detector, as previously described [31]. …”

Section: Methodsmentioning

confidence: 99%

“…N-NO-IQ activation by simulated inflame-matory conditions generates the azo compound 2,2′-azo-3,3′-dimethylimidazo[4,5- f ]quinoline [30], which suggests that a nitrenium ion may be formed as a reactive intermediate. The N-nitroso compounds formed from IQ and MeIQx react with nucleophiles such as azide (although not appreciably with glutathione) and form covalent adducts with DNA [29, 31]. Enzymatic nitrosation has also been observed.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Activation of aminoimidazole carcinogens by nitrosation: Mutagenicity and nucleotide adducts

Zenser

Lakshmi

Schut

et al. 2009

Mutation Research/Genetic Toxicology and Environmental Mutagene

Self Cite

View full text Add to dashboard Cite

Abstract2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazo [4,5-f] quinoxaline (MeIQx) are heterocyclic amines (HCA) derived from high temperature cooking of meat and thought to cause colon cancer in humans. Reactive nitrogen oxygen species, which are mediators of the inflammatory response, can convert these amines to the corresponding N-nitrosamines, N-NO-IQ and N-NO-MeIQx. This study was designed to evaluate whether these N-nitrosamines are genotoxic and could be responsible, in part, for the high incidence of colon cancer in individuals with colitis. Such an association would counsel reduced intake of well-done red meat by colitis patients. Mutagenicity was evaluated by reversion of a lacZ frameshift allele in three different E. coli strains. Strains DJ701 and DJ702 express recombinant (S. typhimurium) aromatic amine N-acetyltransferase; DJ702 also expresses recombinant human cytochrome P450 1A2 and NADPH-P450 reductase; and DJ2002 served as an N-acetyltransferase-negative control. In strain DJ701, N-NO-IQ and N-NOMeIQx elicited dose-dependent mutagenicity, which was not further increased in DJ702. Neither nitrosamine was mutagenic in strain DJ2002. While both N-nitrosamines are stable for >4 hours (pH 7.4, 37°C), they react with DNA or 2′-deoxyguanosine 3′-monophosphate at lower pH (5.5) to form adducts. HOCl, a component of the inflammatory response, increased adduct formation, as measured by 32 P-postlabeling. Following treatment with nuclease P1 and separation by two-dimensional thinlayer chromatography and then HPLC, N-NO-IQ and N-NO-MeIQx were shown to form the same adducts as those formed by N-OH-MeIQx or N-OH-IQ, namely N-(deoxyguanosin-8-yl) adducts. In summary, these N-nitrosamines are genotoxic and might be alternatives to their hydroxylamine analogues as activated intermediates leading to initiation of colon cancer in individuals with colitis.

show abstract

Heterocyclic Aromatic Amines

Turesky

2008

Process‐Induced Food Toxicants

View full text Add to dashboard Cite

2-Nitrosoamino-3-methylimidazo[4,5-f]quinoline activated by the inflammatory response forms nucleotide adducts

Cited by 11 publications

References 52 publications

Dose-dependent reduction of 3,2′-dimethyl-4-aminobiphenyl-derived DNA adducts in colon and liver of rats administered celecoxib

Dose-dependent reduction of 3,2′-dimethyl-4-aminobiphenyl-derived DNA adducts in colon and liver of rats administered celecoxib

Activation of aminoimidazole carcinogens by nitrosation: Mutagenicity and nucleotide adducts

Heterocyclic Aromatic Amines

Contact Info

Product

Resources

About