ArticleThe Journal of pharmacology and experimental therapeutics2010
Codominant expression of N-acetylation and O-acetylation activities catalyzed by N-acetyltransferase 2 in human hepatocytes.
Article in The Journal of pharmacology and experimental therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Causal associations between circulating metabolites and chronic kidney disease: a Mendelian randomization study.Renal failure · 2025Article
- Mini-review: Human N-acetyltransferase genetic polymorphisms in susceptibility to aromatic amine and alkylaniline genotoxicity.The Journal of pharmacology and experimental therapeutics · 2025Review
- Metabolism and genotoxicity of 4,4'-oxydianiline is dependent on N-acetyltransferase 2 genetic polymorphism.Environmental toxicology and pharmacology · 2025Article
- Metabolic effects of heterocyclic amines on insulin‑induced AKT phosphorylation and gluconeogenic gene expression are modified by N -acetyltransferase 2 genetic polymorphism.Pharmacogenetics and genomics · 2025Article
- The effect of the rs1799931 G857A (G286E) polymorphism on N-acetyltransferase 2-mediated carcinogen metabolism and genotoxicity differs with heterocyclic amine exposure.Archives of toxicology · 2023Article
- N-acetyltransferase 2 genetic polymorphism modifies genotoxic and oxidative damage from new psychoactive substances.Archives of toxicology · 2023Article
- Hexavalent chromium increases the metabolism and genotoxicity of aromatic amine carcinogens 4-aminobiphenyl and β-naphthylamine in immortalized human lung epithelial cells.Toxicology and applied pharmacology · 2022Article
- Expression of arylamine N-acetyltransferase 2 activity in immortalized human bronchial epithelial cells.Toxicology and applied pharmacology · 2022Article
- HumanFrontiers in pharmacology · 2022Article
- Acetyl coenzyme A kinetic studies onFrontiers in pharmacology · 2022Article
- Arylamine N-acetyltransferase acetylation polymorphisms: paradigm for pharmacogenomic-guided therapy- a focused review.Expert opinion on drug metabolism & toxicology · 2021Review
- Article
- Human arylamine N-acetyltransferase 2 genotype-dependent protein expression in cryopreserved human hepatocytes.Scientific reports · 2020Article
- Role of Human N-Acetyltransferase 2 Genetic Polymorphism on Aromatic Amine Carcinogen-Induced DNA Damage and Mutagenicity in a Chinese Hamster Ovary Cell Mutation Assay.Environmental and molecular mutagenesis · 2020Article
- Expression and genotype-dependent catalytic activity of N-acetyltransferase 2 (NAT2) in human peripheral blood mononuclear cells and its modulation by Sirtuin 1.Biochemical pharmacology · 2018Article
- Role of N-acetyltransferase 2 acetylation polymorphism in 4, 4'-methylene bis (2-chloroaniline) biotransformation.Toxicology letters · 2018Article
- Catalytic properties and heat stabilities of novel recombinant human N-acetyltransferase 2 allozymes support existence of genetic heterogeneity within the slow acetylator phenotype.Archives of toxicology · 2017Article
- Genetic heterogeneity among slow acetylator N-acetyltransferase 2 phenotypes in cryopreserved human hepatocytes.Archives of toxicology · 2017Article
- ArylamineActa pharmaceutica Sinica. B · 2017Article
- Role of the N-acetylation polymorphism in solithromycin metabolism.Pharmacogenomics · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Human populations exhibit genetic polymorphism in N-acetylation capacity, catalyzed by N-acetyltransferase 2 (NAT2). We investigated the relationship between NAT2 acetylator genotype and phenotype in cryopreserved human hepatocytes. NAT2 genotypes determined in 256 human samples were assigned as rapid (two rapid alleles), intermediate (one rapid and one slow allele), or slow (two slow alleles) acetylator phenotypes based on functional characterization of the NAT2 alleles reported previously in recombinant expression systems. A robust and significant relationship was observed between deduced NAT2 phenotype (rapid, intermediate, or slow) and N-acetyltransferase activity toward sulfamethazine (p < 0.0001) and 4-aminobiphenyl (p < 0.0001) and for O-acetyltransferase-catalyzed metabolic activation of N-hydroxy-4-aminobiphenyl (p < 0.0001), N-hydroxy-2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (p < 0.01), and N-hydroxy-2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (p < 0.0001). NAT2-specific protein levels also significantly associated with the rapid, intermediate, and slow NAT2 acetylator phenotypes (p < 0.0001). As a negative control, p-aminobenzoic acid (an N-acetyltransferase 1-selective substrate) N-acetyltransferase activities from the same samples did not correlate with the three NAT2 acetylator phenotypes (p > 0.05). These results clearly document codominant expression of human NAT2 alleles resulting in rapid, intermediate, and slow acetylator phenotypes. The three phenotypes reflect levels of NAT2 protein catalyzing both N- and O-acetylation. Our results suggest a significant role of NAT2 acetylation polymorphism in arylamine-induced cancers and are consistent with differential cancer risk and/or drug efficacy/toxicity in intermediate compared with rapid or slow NAT2 acetylator phenotypes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.