Differences in β-naphthylamine metabolism and toxicity in Chinese hamster ovary cell lines transfected with human CYP1A2 and NAT2*4, NAT2*5B or NAT2*7B N-acetyltransferase 2 haplotypes

Habil, Mariam R.; Salazar‐González, Raúl A.; Doll, Mark A.; Hein, David W.

doi:10.1007/s00204-022-03367-2

Cited by 7 publications

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“…NAT1 haplotypes were determined by allele specific polymerase chain reaction as previously described ( Doll and Hein, 2002 ). Quantitative RT-PCR (RT-qPCR) assays were used to assess the relative amount of CYP1A2 mRNA in cells in CHO cells and CYP1A2 protein expression was measured using in cell western protocol as previously described ( Habil et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

Acetyl coenzyme A kinetic studies on N-acetylation of environmental carcinogens by human N-acetyltransferase 1 and its NAT1*14B variant

Habil

Doll²,

Hein³

2022

Front. Pharmacol.

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N-acetyltransferase 1 (NAT1) is a xenobiotic metabolizing enzyme that uses acetyl coenzyme A (AcCoA) as a cofactor for N-acetylation of many carcinogens including aromatic amines and alkylanilines. NAT1 is characterized by single nucleotide polymorphisms (SNPs) that may modulate affinity towards AcCoA. In the current study, we used Chinese hamster ovary (CHO) cells stably transfected with human NAT1*4 (reference allele) or NAT1*14B (variant allele) to measure AcCoA kinetic parameters for N-acetyltransferase activity measurements towards p-aminobenzoic acid (PABA), 4-aminobiphenyl (4-ABP), β-naphthylamine (BNA), benzidine and 3,4-dimethylaniline (3,4-DMA). Our results showed higher N-acetylation rates for each substrate catalyzed by NAT1*4 compared to NAT1*14B. NAT1*4 exhibited higher affinity to AcCoA when catalyzing the N-acetylation of BNA and benzidine compared to NAT1*14B. The results of the current study provide further insights into differences in carcinogen metabolism among individuals possessing the NAT1*14B haplotype.

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Section: Methodsmentioning

confidence: 99%