UGT bioactivation of AαC
نویسندگان
چکیده
Background: 2-Amino-9H-pyrido[2,3-b]indole (AαC) is a carcinogen formed in tobacco smoke, but little is known about its metabolism in humans. Result: UDP-Glucuronosyltransferases catalyze the binding of N-oxidized-AαC to DNA. Conclusion: Glucuronidation, normally a detoxication pathway, contributes to the genotoxicity of AαC. Significance: The exposure to and UGTbioactivation of AαC provides a biochemical mechanism for the elevated risk of liver and digestive tract cancers in smokers.
منابع مشابه
2-Amino-9H-pyrido[2,3-b]indole (AαC) Adducts and Thiol Oxidation of Serum Albumin as Potential Biomarkers of Tobacco Smoke.
2-Amino-9H-pyrido[2,3-b]indole (AαC) is a carcinogenic heterocyclic aromatic amine formed during the combustion of tobacco. AαC undergoes bioactivation to form electrophilic N-oxidized metabolites that react with DNA to form adducts, which can lead to mutations. Many genotoxicants and toxic electrophiles react with human serum albumin (albumin); however, the chemistry of reactivity of AαC with ...
متن کاملCharacterization of AαC-serum albumin adducts 2-Amino-9H-pyrido[2,3-b]indole (AαC) Adducts and Thiol Oxidation of Serum Albumin as Potential Biomarkers of Tobacco Smoke
2-Amino-9H-pyrido[2-3-b]indole (AαC) is a carcinogenic heterocyclic aromatic amine (HAA) formed during the combustion of tobacco. AαC undergoes bioactivation to form electrophilic Noxidized metabolites that react with DNA to form adducts, which can lead to mutations. Many genotoxicants and toxic electrophiles react with human serum albumin (albumin); however, the chemistry of reactivity of AαC ...
متن کاملGenoprotection by UDP-Glucuronosyltransferases in Peroxidase-dependent, Reactive Oxygen Species-mediated Micronucleus Initiation by the Carcinogens 4-(Methylnitrosamino)-1 -(3-pyridy 1)-1-butanone and Benzofajpyrene1
UDP-glucuronosyltransferases (UGTs) catalyze the glucuronidation and elimination of putative tobacco carcinogens such as benzo[a]pyrene (B[a]P) and 4-(methylnitrosarnino)-l-(3-pyridyl)-l-butanone (NNK), which may reduce competing bioactivation and toxicity. B[a]P-initiated cytotoxicity and micronucleus formation, believed to reflect carcinogenic initiation, are enhanced in UGT-deficient rat fib...
متن کاملA mechanistic approach to understanding species differences in felbamate bioactivation: relevance to drug-induced idiosyncratic reactions.
In an attempt to understand the species-selective toxicity of felbamate (2-phenyl-1,3-propanediol dicarbamate, FBM), which is thought to result from bioactivation to 2-phenylpropenal, FBM metabolism was evaluated in rats and humans. The formation of 2-phenylpropenal was monitored by the amount of its mercapturates excreted in urine. The data show a relative 5-fold increase in mercapturate excre...
متن کاملDNA 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.
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 A...
متن کامل