Linked Life Data

11505221

Source:http://linkedlifedata.com/resource/pubmed/id/11505221

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-8-15
pubmed:abstractText
N-acetyltransferase 1 (NAT1) catalyses the activation and/or deactivation of aromatic and heterocyclic amine carcinogens. A genetic polymorphism in NAT1 is associated with an increased risk of various cancers and drug toxicities, but epidemiological investigations are severely compromised by a poor understanding of the relationship between NAT1 genotype and phenotype. Human reference NAT1*4 and 12 known human NAT1 allelic variants possessing nucleotide polymorphisms in the NAT1 coding region were cloned and expressed in yeast (Schizosaccharomyces pombe). Large reductions in N- and O-acetyltransferase catalytic activities were observed for recombinant NAT1 allozymes encoded by NAT1*14B, NAT1*15, NAT1*17, NAT1*19 and NAT1*22. Each of these alleles exhibited NAT1 protein expression levels below the limit of detection as measured by Western blot. No differences between high and low activity NAT1 alleles were observed in relative mRNA expression or relative transformation efficiency. The recombinant NAT1 17 and NAT1 22 allozymes showed reduced intrinsic stability when compared with NAT1 4. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) N-acetylation was not catalysed by any of the NAT1 allozymes. Large differences in the metabolic activation via O-acetylation of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-hydroxy-PhIP) were noted for NAT1 allelic variants. The results of these studies suggest an important role for the NAT1 genetic polymorphism in metabolism of aromatic and heterocyclic amine carcinogens. Furthermore, these results suggest that low NAT1 phenotype results from NAT1 allelic variants that encode reduced expression of NAT1 and/or less-stable NAT1 protein.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0960-314X
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
511-20
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Functional characterization of nucleotide polymorphisms in the coding region of N-acetyltransferase 1.
pubmed:affiliation
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.