Role of N-acetyltransferase 2 acetylation polymorphism in 4, 4′-methylene bis (2-chloroaniline) biotransformation
-
Add time:08/18/2019 Source:sciencedirect.com
Arylamine N-acetyltransferase 1 (NAT1) and 2 (NAT2) catalyze the acetylation of arylamine carcinogens. Single nucleotide polymorphisms in the NAT2 coding exon present in NAT2 haplotypes encode allozymes with reduced N-acetyltransferase activity towards the N-acetylation of arylamine carcinogens and the O-acetylation of their N-hydroxylated metabolites. NAT2 acetylator phenotype modifies urinary bladder cancer risk following exposures to arylamine carcinogens such as 4-aminobiphenyl. 4, 4′-methylene bis (2-chloroaniline) (MOCA) is a Group 1 carcinogen for which a role of the NAT2 acetylation polymorphism on cancer risk is unknown. We investigated the role of NAT2 and the genetic acetylation polymorphism on both MOCA N-acetylation and N-hydroxy-MOCA O-acetylation. MOCA N-acetylation exhibited a robust gene dose response in rabbit liver cytosol and in cryopreserved human hepatocytes derived from individuals of rapid, intermediate and slow acetylator NAT2 genotype. MOCA exhibited about 4-fold higher affinity for recombinant human NAT2 than NAT1. Recombinant human NAT2*4 (reference) and 15 variant recombinant human NAT2 allozymes catalyzed both the N-acetylation of MOCA and the O-acetylation of N-hydroxy-MOCA. Human NAT2 5, NAT2 6, NAT2 7 and NAT2 14 allozymes catalyzed MOCA N-acetylation and N-hydroxy-O-acetylation at rates much lower than the reference NAT2 4 allozyme. In conclusion, our results show that NAT2 acetylator genotype has an important role in MOCA metabolism and suggest that risk assessments related to MOCA exposures consider accounting for NAT2 acetylator phenotype in the analysis.
We also recommend Trading Suppliers and Manufacturers of 4-Chloroaniline (cas 106-47-8). Pls Click Website Link as below: cas 106-47-8 suppliers
Prev:Removal of chlorobenzene and 1,4-Dichlorobenzene (cas 106-46-7) using novel poly-o-toluidine zirconium(IV) phosphotellurite exchanger
Next:Research paperDetermination of adsorption isotherms of aniline and 4-Chloroaniline (cas 106-47-8) on halloysite adsorbent by inverse liquid chromatography) - 【Back】【Close 】【Print】【Add to favorite 】
- Related Information
- Carbon-nanotube amperometric sensor for selective determination of 4-Chloroaniline (cas 106-47-8) in commercial chlorhexidine solutions08/25/2019
- Sun light degradation of 4-Chloroaniline (cas 106-47-8) in waters and its effect on toxicity. A high performance liquid chromatography – Diode array – Tandem mass spectrometry study08/24/2019
- Sensing properties of BN nanotube toward carcinogenic 4-Chloroaniline (cas 106-47-8): A computational study08/23/2019
- Radiation-induced degradation of 4-Chloroaniline (cas 106-47-8) in aqueous solution08/22/2019
- Biodegradation of 2-chloroaniline, 3-chloroaniline, and 4-Chloroaniline (cas 106-47-8) by a novel strain Delftia tsuruhatensis H108/21/2019
- High-rate biodegradation and metabolic pathways of 4-Chloroaniline (cas 106-47-8) by aerobic granules08/20/2019
- Research paperDetermination of adsorption isotherms of aniline and 4-Chloroaniline (cas 106-47-8) on halloysite adsorbent by inverse liquid chromatography08/19/2019