Chromosomal localization of human genes for arylamine <i>N</i>-acetyltransferase

Hickman, Dean; Risch, Angela; Buckle, VJ; Spurr, N.K.; Jeremiah, Steve; McCarthy, Afshan; Sim, Edith

doi:10.1042/bj2970441

Cited by 108 publications

(62 citation statements)

References 27 publications

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“…Human N-acetyltransferases, NAT1 and NAT2, are major enzymes involved in the final step of metabolism of GLS hydrolysis products, such as ITCs and are polymorphic [211]. For drugs it is well described that different acetylation capacities cause significant differences in drug efficacy and in the susceptibility to certain types of diseases.…”

Section: Effect Of Genetic Polymorphisms On Gls Metabolism and Interimentioning

confidence: 99%

Glucosinolates inBrassicavegetables: The influence of the food supply chain on intake, bioavailability and human health

Verkerk¹,

Schreiner

Krumbein

et al. 2009

Molecular Nutrition Food Res

526

424

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Glucosinolates (GLSs) are found in Brassica vegetables. Examples of these sources include cabbage, Brussels sprouts, broccoli, cauliflower and various root vegetables (e.g. radish and turnip). A number of epidemiological studies have identified an inverse association between consumption of these vegetables and the risk of colon and rectal cancer. Animal studies have shown changes in enzyme activities and DNA damage resulting from consumption of Brassica vegetables or isothiocyanates, the breakdown products (BDP) of GLSs in the body. Mechanistic studies have begun to identify the ways in which the compounds may exert their protective action but the relevance of these studies to protective effects in the human alimentary tract is as yet unproven. In vitro studies with a number of specific isothiocyanates have suggested mechanisms that might be the basis of their chemoprotective effects. The concentration and composition of the GLSs in different plants, but also within a plant (e.g. in the seeds, roots or leaves), can vary greatly and also changes during plant development. Furthermore, the effects of various factors in the supply chain of Brassica vegetables including breeding, cultivation, storage and processing on intake and bioavailability of GLSs are extensively discussed in this paper.

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Section: Effect Of Genetic Polymorphisms On Gls Metabolism and Interimentioning

confidence: 99%

Glucosinolates inBrassicavegetables: The influence of the food supply chain on intake, bioavailability and human health

Verkerk¹,

Schreiner

Krumbein

et al. 2009

Molecular Nutrition Food Res

526

424

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“…NAT1, NAT2 and a pseudogene NATP are located on the short arm of human chromosome 8 NAT2 polymorphism and urinary bladder cancer risk DW Hein (Blum et al, 1990;Hickman et al, 1994) in the orientation NAT1:NATP:NAT2 (Matas et al, 1997). NAT1 and NAT2 share 87% nucleotide homology in the coding region, yielding 55 aminoacid differences.…”

Section: Molecular Geneticsmentioning

confidence: 99%

N-acetyltransferase 2 genetic polymorphism: effects of carcinogen and haplotype on urinary bladder cancer risk

2006

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A role for the N-acetyltransferase 2 (NAT2) genetic polymorphism in cancer risk has been the subject of numerous studies. Although comprehensive reviews of the NAT2 acetylation polymorphism have been published elsewhere, the objective of this paper is to briefly highlight some important features of the NAT2 acetylation polymorphism that are not universally accepted to better understand the role of NAT2 polymorphism in carcinogenic risk assessment. NAT2 slow acetylator phenotype(s) infer a consistent and robust increase in urinary bladder cancer risk following exposures to aromatic amine carcinogens. However, identification of specific carcinogens is important as the effect of NAT2 polymorphism on urinary bladder cancer differs dramatically between monoarylamines and diarylamines. Misclassifications of carcinogen exposure and NAT2 genotype/phenotype confound evidence for a real biological effect. Functional understanding of the effects of NAT2 genetic polymorphisms on metabolism and genotoxicity, tissue-specific expression and the elucidation of the molecular mechanisms responsible are critical for the interpretation of previous and future human molecular epidemiology investigations into the role of NAT2 polymorphism on cancer risk. Although associations have been reported for various cancers, this paper focuses on urinary bladder cancer, a cancer in which a role for NAT2 polymorphism was first proposed and for which evidence is accumulating that the effect is biologically significant with important public health implications.

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“…6,35 Human NAT1 and NAT2, as well as NATP1, have been localised to the short arm of chromosome 8, 6,36 more specifically in region 8p22. 8 The NAT loci are separated by only 170-360 kb and are in the orientation NAT1 → NATP1 → NAT2, with NAT1 being on the centromeric side of marker D8S261 and NAT2 coinciding with marker D8S21. 36 Both NAT1 and NAT2 genes display pronounced allelic variation, with 26 different human NAT1 and 29 different human NAT2 alleles identified to date.…”

Section: Gene Localisation Structure and Expressionmentioning

confidence: 99%

Pharmacogenetics of the arylamine N-acetyltransferases

et al. 2002

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The arylamine N-acetyltransferases (NATs) are involved in the metabolism of a variety of different compounds that we are exposed to on a daily basis. Many drugs and chemicals found in the environment, such as those in cigarette smoke, car exhaust fumes and in foodstuffs, can be either detoxified by NATs and eliminated from the body or bioactivated to metabolites that have the potential to cause toxicity and/or cancer. NATs have been implicated in some adverse drug reactions and as risk factors for several different types of cancers. As a result, the levels of NATs in the body have important consequences with regard to an individual's susceptibility to certain druginduced toxicities and cancers. This review focuses on recent advances in the molecular genetics of the human NATs.

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Chromosomal localization of human genes for arylamine N-acetyltransferase

Cited by 108 publications

References 27 publications

Glucosinolates inBrassicavegetables: The influence of the food supply chain on intake, bioavailability and human health

Glucosinolates inBrassicavegetables: The influence of the food supply chain on intake, bioavailability and human health

N-acetyltransferase 2 genetic polymorphism: effects of carcinogen and haplotype on urinary bladder cancer risk

Pharmacogenetics of the arylamine N-acetyltransferases

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