Molecular Genetics and Epidemiology of the NAT 1 and NAT 2 Acetylation Polymorphisms 1

The focus of this review is the molecular genetics, including consensusNAT1 and NAT2 nomenclature, and cancer epidemiology of theNAT1 and NAT2 acetylation polymorphisms. Two N-acetyltransferase isozymes, NAT1 and NAT2, are polymorphic and catalyze bothNacetylation (usually deactivation) andO-acetylation (usually activation) of aromatic and heterocyclic amine carcinogens. Epidemiological studies suggest that the NAT1 and NAT2 acetylation polymorphisms modify risk of developing urinary bladder, colorectal, breast, head and neck, lung, and possibly prostate cancers. Associations between slowNAT2 acetylator genotypes and urinary bladder cancer and between rapid NAT2 acetylator genotypes and colorectal cancer are the most consistently reported. The individual risks associated with NAT1 and/or NAT2 acetylator genotypes are small, but they increase when considered in conjunction with other susceptibility genes and/or aromatic and heterocyclic amine carcinogen exposures. Because of the relatively high frequency of someNAT1 and NAT2 genotypes in the population, the attributable cancer risk may be high. The effect of NAT1 and NAT2 genotype on cancer risk varies with organ site, probably reflecting tissue-specific expression of NAT1 and NAT2. Ethnic differences exist in NAT1 and NAT2 genotype frequencies that may be a factor in cancer incidence. Large-scale molecular epidemiological studies that investigate the role of NAT1 and NAT2 genotypes and/or phenotypes together with other genetic susceptibility gene polymorphisms and biomarkers of carcinogen exposure are necessary to expand our current understanding of the role of NAT1 and NAT2 acetylation polymorphisms in cancer risk.

[1]  D. Grant,et al.  Update on consensus arylamine N-acetyltransferase gene nomenclature. , 2000, Pharmacogenetics.

[2]  D. Hein.  N-Acetyltransferase genetics and their role in predisposition to aromatic and heterocyclic amine-induced carcinogenesis. , 2000, Toxicology letters.

[3]  R. MacArthur,et al.  Acetylator phenotype and genotype in patients infected with HIV: discordance between methods for phenotype determination and genotype. , 2000, Pharmacogenetics.

[4]  M. Wargovich,et al.  Association between acetylator genotype and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) DNA adduct formation in colon and prostate of inbred Fischer 344 and Wistar Kyoto rats. , 2000, Cancer letters.

[5]  M. Ingelman-Sundberg,et al.  Genetic epidemiology of environmental toxicity and cancer susceptibility: human allelic polymorphisms in drug-metabolizing enzyme genes, their functional importance, and nomenclature issues. , 1999, Drug metabolism reviews.

[6]  J. Brockmöller,et al.  Arylamine N-acetyltransferase activity in man. , 1999, Drug metabolism reviews.

[7]  M. Doll,et al.  Novel Human N-Acetyltransferase 2 Alleles That Differ in Mechanism for Slow Acetylator Phenotype* , 1999, The Journal of Biological Chemistry.

[8]  P. Dayer,et al.  Role of arylamine N-acetyltransferase 1 and 2 (NAT1 and NAT2) genotypes in susceptibility to oral/pharyngeal and laryngeal cancers. , 1999, Pharmacogenetics.

[9]  J. Basilion,et al.  Single-nucleotide polymorphisms can cause different structural folds of mRNA. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[10]  T. Rustan,et al.  Prostate-specific human N-acetyltransferase 2 (NAT2) expression in the mouse. , 1999, The Journal of pharmacology and experimental therapeutics.

[11]  C. Junien,et al.  Candidate genetic modifiers of individual susceptibility to renal cell carcinoma: a study of polymorphic human xenobiotic-metabolizing enzymes. , 1999, Cancer research.

[12]  C. Wadelius,et al.  Polymorphisms in NAT2, CYP2D6, CYP2C19 and GSTP1 and their association with prostate cancer. , 1999, Pharmacogenetics.

[13]  T. Kawamoto,et al.  Arylamine N-acetyltransferase 1 (NAT1) and 2 (NAT2) genes and risk of urothelial transitional cell carcinoma among Japanese. , 1999, Pharmacogenetics.

[14]  D. Hein,et al.  Higher DNA adduct levels in urinary bladder and prostate of slow acetylator inbred rats administered 3,2'-dimethyl-4-aminobiphenyl. , 1999, Toxicology and applied pharmacology.

[15]  I. Georgiou,et al.  Genotypes of N-acetyltransferase-2 and risk of bladder cancer: a case-control study. , 1999, The Journal of urology.

[16]  J. Cerhan,et al.  N-acetyltransferase 1 genetic polymorphism, cigarette smoking, well-done meat intake, and breast cancer risk. , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[17]  M. Yano,et al.  Genetic polymorphisms of drug‐metabolizing enzymes and susceptibility to head‐and‐neck squamous‐cell carcinoma , 1999, International journal of cancer.

[18]  H. Ito,et al.  N-acetyltransferase 1 genetic polymorphism influences the risk of prostate cancer development. , 1999, Cancer letters.

[19]  I. Roots,et al.  Pitfalls in N-acetyltransferase 2 genotyping. , 1999, Pharmacogenetics.

[20]  T. Kunkel,et al.  Symposium overview: the role of genetic polymorphism and repair deficiencies in environmental disease. , 1999, Toxicological sciences : an official journal of the Society of Toxicology.

[21]  I. Roots,et al.  Association of arylamine N-acetyltransferases NAT1 and NAT2 genotypes to laryngeal cancer risk. , 1999, Pharmacogenetics.

[22]  D. Phillips,et al.  DNA adducts in human breast tissue: association with N-acetyltransferase-2 (NAT2) and NAT1 genotypes. , 1998, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[23]  J. Prados,et al.  Expression in human prostate of drug- and carcinogen-metabolizing enzymes: association with prostate cancer risk. , 1998, British Journal of Cancer.

[24]  Y. Doki,et al.  Association between genetic polymorphisms of glutathione S‐transferase P1 and N‐acetyltransferase 2 and susceptibility to squamous‐cell carcinoma of the esophagus , 1998, International journal of cancer.

[25]  E. Sim,et al.  Placental expression of arylamine N-acetyltransferases: evidence for linkage disequilibrium between NAT1*10 and NAT2*4 alleles of the two human arylamine N-acetyltransferase loci NAT1 and NAT2. , 1998, Pharmacology & toxicology.

[26]  D. Bell,et al.  A pilot study testing the association between N-acetyltransferases 1 and 2 and risk of oral squamous cell carcinoma in Japanese people. , 1998, Carcinogenesis.

[27]  K. Hemminki,et al.  Glutathione S-transferase mu1 and N-acetyltransferase 2 genetic polymorphisms and exposure to tobacco smoke in nonsmoking and smoking lung cancer patients and population controls. , 1998, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[28]  Jack A. Taylor,et al.  The role of N-acetylation polymorphisms in smoking-associated bladder cancer: evidence of a gene-gene-exposure three-way interaction. , 1998, Cancer research.

[29]  W C Willett,et al.  A prospective study of N-acetyltransferase genotype, red meat intake, and risk of colorectal cancer. , 1998, Cancer research.

[30]  N. Probst-Hensch,et al.  Variants of N-acetyltransferase NAT1 and a case-control study of colorectal adenomas. , 1998, Pharmacogenetics.

[31]  R. Millikan,et al.  Cigarette smoking, N-acetyltransferases 1 and 2, and breast cancer risk. , 1998, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[32]  J. Ware,et al.  Cellular distribution of N-acetyltransferase activity in the rat small intestine. , 1998, Biochemical pharmacology.

[33]  V. Álvarez,et al.  Genetic polymorphism of N-acetyltransferase-2, glutathione S-transferase-M1, and cytochromes P450IIE1 and P450IID6 in the susceptibility to head and neck cancer. , 1998, Journal of clinical pathology.

[34]  R. Sinha,et al.  Breast cancer risk, meat consumption and N‐acetyltransferase (NAT2) genetic polymorphisms , 1998, International journal of cancer.

[35]  G. Fakis,et al.  Expression of arylamine N-acetyltransferase in human intestine , 1998, Gut.

[36]  R. Minchin,et al.  Functional polymorphism of the human arylamine N-acetyltransferase type 1 gene caused by C190T and G560A mutations. , 1998, Pharmacogenetics.

[37]  E. Sim,et al.  Genotyping human arylamine N-acetyltransferase type 1 (NAT1): the identification of two novel allelic variants. , 1998, Biochemical pharmacology.

[38]  D. Grant,et al.  Identification and characterization of variant alleles of human acetyltransferase NAT1 with defective function using p-aminosalicylate as an in-vivo and in-vitro probe. , 1998, Pharmacogenetics.

[39]  D. Bell,et al.  Pilot study of free and conjugated urinary mutagenicity during consumption of pan-fried meats: possible modulation by cruciferous vegetables, glutathione S-transferase-M1, and N-acetyltransferase-2. , 1997, Mutation research.

[40]  A. Deitz,et al.  A restriction fragment length polymorphism assay that differentiates human N-acetyltransferase-1 (NAT1) alleles. , 1997, Analytical biochemistry.

[41]  T. Rustan,et al.  Higher frequency of aberrant crypt foci in rapid than slow acetylator inbred rats administered the colon carcinogen 3,2'-dimethyl-4-aminobiphenyl. , 1997, Toxicology and applied pharmacology.

[42]  J. Manson,et al.  A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer. , 1997, Carcinogenesis.

[43]  S R Tannenbaum,et al.  Urinary excretion of unmetabolized and phase II conjugates of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in humans: relationship to cytochrome P4501A2 and N-acetyltransferase activity. , 1997, Cancer research.

[44]  C. Smith,et al.  N-acetyltransferase 2 genotype in colorectal cancer and selective gene retention in cancers with chromosome 8p deletions , 1997, Gut.

[45]  A. Daly,et al.  Relationship between acetylator status, smoking, and diet and colorectal cancer risk in the north-east of England. , 1997, Carcinogenesis.

[46]  A. Risch,et al.  Mapping AAC1, AAC2 and AACP, the genes for arylamine N-acetyltransferases, carcinogen metabolising enzymes on human chromosome 8p22, a region frequently deleted in tumours. , 1997, Cytogenetics and cell genetics.

[47]  N. Lang.  Acetylation as an indicator of risk. , 1997, Environmental health perspectives.

[48]  D. Grant,et al.  Human acetyltransferase polymorphisms. , 1997, Mutation research.

[49]  T. Rustan,et al.  Rodent models of the human acetylation polymorphism: comparisons of recombinant acetyltransferases. , 1997, Mutation research.

[50]  D. Grant,et al.  The role of xenobiotic metabolizing enzymes in arylamine toxicity and carcinogenesis: functional and localization studies. , 1997, Mutation research.

[51]  T. Rustan,et al.  Identification of a novel allele at the human NAT1 acetyltransferase locus. , 1997, Biochemical and biophysical research communications.

[52]  J. Potter,et al.  Determination of human NAT2 acetylator genotype by oligonucleotide ligation assay. , 1997, BioTechniques.

[53]  I. Mills,et al.  Localization of polymorphic N-acetyltransferase (NAT2) in tissues of inbred mice. , 1997, Pharmacogenetics.

[54]  D. Grant,et al.  Study of the role of the highly conserved residues Arg9 and Arg64 in the catalytic function of human N-acetyltransferases NAT1 and NAT2 by site-directed mutagenesis. , 1997, The Biochemical journal.

[55]  H. Okkels,et al.  Arylamine N-acetyltransferase 1 (NAT1) and 2 (NAT2) polymorphisms in susceptibility to bladder cancer: the influence of smoking. , 1997, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[56]  M. Doll,et al.  Cloning, sequencing, and recombinant expression of NAT1, NAT2, and NAT3 derived from the C3H/HeJ (rapid) and A/HeJ (slow) acetylator inbred mouse: functional characterization of the activation and deactivation of aromatic amine carcinogens. , 1997, Toxicology and applied pharmacology.

[57]  R. Bayoumi,et al.  A new mutation C759T in the polymorphic N-acetyltransferase (NAT2) gene. , 1997, Pharmacogenetics.

[58]  K. Koskinen,et al.  Glutathione S-transferase and N-acetyltransferase genotypes and asbestos-associated pulmonary disorders. , 1996, Journal of the National Cancer Institute.

[59]  U. Meyer,et al.  Increased risk for hepatocellular carcinoma in NAT2-slow acetylators and CYP2D6-rapid metabolizers. , 1996, Pharmacogenetics.

[60]  J. Freudenheim,et al.  Cigarette smoking, N-acetyltransferase 2 genetic polymorphisms, and breast cancer risk. , 1996, JAMA.

[61]  D. Hein,et al.  2-Aminofluorene-DNA adduct levels in tumor-target and nontarget organs of rapid and slow acetylator Syrian hamsters congenic at the NAT2 locus. , 1996, Toxicology and applied pharmacology.

[62]  J. Ware,et al.  Longitudinal distribution of arylamine N-acetyltransferases in the intestine of the hamster, mouse, and rat. Evidence for multiplicity of N-acetyltransferases in the intestine. , 1996, Biochemical pharmacology.

[63]  J. Benítez,et al.  Identification and prevalence study of 17 allelic variants of the human NAT2 gene in a white population. , 1996, Pharmacogenetics.

[64]  T. Rustan,et al.  Human N-acetylation of benzidine: role of NAT1 and NAT2. , 1996, Cancer research.

[65]  J. Brockmöller,et al.  Homozygous rapid arylamine N-acetyltransferase (NAT2) genotype as a susceptibility factor for lung cancer. , 1996, Cancer research.

[66]  L. Stanley,et al.  Immunochemical detection of arylamine N-acetyltransferase in normal and neoplastic bladder. , 1996, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[67]  J. Brockmöller,et al.  Combined analysis of inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1, microsomal epoxide hydrolase, and cytochrome P450 enzymes as modulators of bladder cancer risk. , 1996, Cancer research.

[68]  C. Davis,et al.  N-acetyltransferase expression and metabolic activation of the food-derived heterocyclic amines in the human mammary gland. , 1996, Cancer research.

[69]  J. Brockmöller,et al.  NAT2*12A (803A-->G) codes for rapid arylamine n-acetylation in humans. , 1996, Pharmacogenetics.

[70]  A. McMichael,et al.  Diet, acetylator phenotype, and risk of colorectal neoplasia , 1996, The Lancet.

[71]  J. Brockmöller,et al.  Determination and allelic allocation of seven nucleotide transitions within the arylamine N‐acetyltransferase gene in the Polish population , 1996, Clinical pharmacology and therapeutics.

[72]  D. Grant,et al.  Genotyping of the polymorphic N-acetyltransferase (NAT2*) gene locus in two native African populations. , 1996, Pharmacogenetics.

[73]  J. Alexander,et al.  Effect of acetylator genotype on 3,2'-dimethyl-4-aminobiphenyl induced aberrant crypt foci in the colon of hamsters. , 1996, Carcinogenesis.

[74]  T. Rustan,et al.  Cloning, expression, and functional characterization of rapid and slow acetylator polymorphic N-acetyl-transferase encoding genes of the Syrian hamster. , 1996, Pharmacogenetics.

[75]  T. P. Pretlow,et al.  Acetylator genotype (NAT2)-dependent formation of aberrant crypts in congenic Syrian hamsters administered 3,2'-dimethyl-4-aminobiphenyl. , 1996, Cancer research.

[76]  C. Smith,et al.  Polymorphisms in drug-metabolizing enzymes as modifiers of cancer risk. , 1995, Clinical chemistry.

[77]  W. Weber,et al.  Slow acetylation in mice is caused by a labile and catalytically impaired mutant N-acetyltransferase (NAT2 9). , 1995, Drug metabolism and disposition: the biological fate of chemicals.

[78]  D. Bell,et al.  Role of aromatic amine acetyltransferases, NAT1 and NAT2, in carcinogen-DNA adduct formation in the human urinary bladder. , 1995, Cancer research.

[79]  A. Deitz,et al.  Determination of human NAT2 acetylator genotype by restriction fragment-length polymorphism and allele-specific amplification. , 1995, Analytical biochemistry.

[80]  J. Brockmöller,et al.  Arylamine N-acetyltransferase (NAT2) mutations and their allelic linkage in unrelated Caucasian individuals: correlation with phenotypic activity. , 1995, American journal of human genetics.

[81]  J. Unadkat,et al.  Enzyme kinetic properties of human recombinant arylamine N-acetyltransferase 2 allotypic variants expressed in Escherichia coli. , 1995, Biochemical pharmacology.

[82]  T. Rustan,et al.  Metabolic activation of N-hydroxyarylamines and N-hydroxyarylamides by 16 recombinant human NAT2 allozymes: effects of 7 specific NAT2 nucleic acid substitutions. , 1995, Cancer research.

[83]  J. Benítez,et al.  Lung cancer and mutations at the polymorphic NAT2 gene locus. , 1995, Pharmacogenetics.

[84]  K. Pelin,et al.  Inherited GSTM1 and NAT2 defects as concurrent risk modifiers in asbestos-related human malignant mesothelioma. , 1995, Cancer research.

[85]  E. Sim,et al.  Purification of recombinant human N-acetyltransferase type 1 (NAT1) expressed in E. coli and characterization of its potential role in folate metabolism. , 1995, Biochemical pharmacology.

[86]  M. Longnecker,et al.  Acetylation polymorphism and prevalence of colorectal adenomas. , 1995, Cancer research.

[87]  R. Minchin.  Acetylation of p-aminobenzoylglutamate, a folic acid catabolite, by recombinant human arylamine N-acetyltransferase and U937 cells. , 1995, The Biochemical journal.

[88]  G. Steineck,et al.  Effect of cooking temperature on the formation of heterocyclic amines in fried meat products and pan residues. , 1995, Carcinogenesis.

[89]  A. Risch,et al.  Slow N-acetylation genotype is a susceptibility factor in occupational and smoking related bladder cancer. , 1995, Human molecular genetics.

[90]  D. Gaylor,et al.  Limitations of probit plots in pharmacogenetics: requirement of genetic analyses to test hypotheses based on graphical methods. , 1995, Pharmacogenetics.

[91]  M. Relling,et al.  Nomenclature for N-acetyltransferases. , 1995, Pharmacogenetics.

[92]  K. Shibuta,et al.  Molecular genotyping for N‐acetylation polymorphism in Japanese patients with colorectal cancer , 1994, Cancer.

[93]  E. Messing,et al.  Expression of N-acetyltransferase (NAT) in cultured human uroepithelial cells. , 1994, Carcinogenesis.

[94]  M A Butler,et al.  Rapid metabolic phenotypes for acetyltransferase and cytochrome P4501A2 and putative exposure to food-borne heterocyclic amines increase the risk for colorectal cancer or polyps. , 1994, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[95]  Fccp P. G. PharmD,et al.  Genetic Factors in Drug Therapy: Clinical and Molecular Pharmacogenetics , 1994 .

[96]  S. Kelly,et al.  Arylamine N-acetyltransferase in Balb/c mice: identification of a novel mouse isoenzyme by cloning and expression in vitro. , 1994, The Biochemical journal.

[97]  J. Benítez,et al.  Molecular analysis of the arylamine N‐acetyltransferase polymorphism in a Spanish population , 1994, Clinical pharmacology and therapeutics.

[98]  R. Isbrucker,et al.  Acetylator phenotyping: the urinary caffeine metabolite ratio in slow acetylators correlates with a marker of systemic NAT1 activity. , 1994, Pharmacogenetics.

[99]  B. Lin,et al.  Ethnic distribution of slow acetylator mutations in the polymorphic N-acetyltransferase (NAT2) gene. , 1994, Pharmacogenetics.

[100]  B. Henderson,et al.  Acetylator phenotype, aminobiphenyl-hemoglobin adduct levels, and bladder cancer risk in white, black, and Asian men in Los Angeles, California. , 1994, Journal of the National Cancer Institute.

[101]  T. Rustan,et al.  Cloning, expression, and functional characterization of two mutant (NAT2(191) and NAT2(341/803)) and wild-type human polymorphic N-acetyltransferase (NAT2) alleles. , 1994, Drug metabolism and disposition: the biological fate of chemicals.

[102]  T. Rustan,et al.  Molecular genetics of human polymorphic N-acetyltransferase: enzymatic analysis of 15 recombinant wild-type, mutant, and chimeric NAT2 allozymes. , 1994, Human molecular genetics.

[103]  T. Rustan,et al.  Syrian hamster monomorphic N-acetyltransferase (NAT1) alleles: amplification, cloning, sequencing, and expression in E. coli. , 1994, Pharmacogenetics.

[104]  R. Kato,et al.  Primary structure and molecular basis of polymorphic appearance of an acetyltransferase (AT-II)* in hamsters. , 1994, Pharmacogenetics.

[105]  M. Doll,et al.  Polymorphic arylamine N-acetyltransferase encoding gene (NAT2) from homozygous rapid and slow acetylator congenic Syrian hamsters. , 1994, Gene.

[106]  A. Risch,et al.  Chromosomal localization of human genes for arylamine N-acetyltransferase. , 1994, The Biochemical journal.

[107]  J G Chung,et al.  Distribution of 2-aminofluorene and p-aminobenzoic acid N-acetyltransferase activity in tissues of C57BL/6J rapid and B6.A-NatS slow acetylator congenic mice. , 1993, Drug metabolism and disposition: the biological fate of chemicals.

[108]  D. Grant,et al.  Metabolic activation and deactivation of arylamine carcinogens by recombinant human NAT1 and polymorphic NAT2 acetyltransferases. , 1993, Carcinogenesis.

[109]  Jack A. Taylor,et al.  Genotype/phenotype discordance for human arylamine N-acetyltransferase (NAT2) reveals a new slow-acetylator allele common in African-Americans. , 1993, Carcinogenesis.

[110]  R. Hayes,et al.  (Continued on next page) , 1934 .

[111]  R. Hayes,et al.  N-acetylation phenotype and genotype and risk of bladder cancer in benzidine-exposed workers. , 1993, Carcinogenesis.

[112]  B. Lin,et al.  Slow acetylator mutations in the human polymorphic N-acetyltransferase gene in 786 Asians, blacks, Hispanics, and whites: application to metabolic epidemiology. , 1993, American journal of human genetics.

[113]  T. Deguchi,et al.  The structure and characteristics of a fourth allele of polymorphic N-acetyltransferase gene found in the Japanese population. , 1993, Biochemical and biophysical research communications.

[114]  W. Weber,et al.  Structural heterogeneity of Caucasian N-acetyltransferase at the NAT1 gene locus. , 1993, Archives of biochemistry and biophysics.

[115]  T. Rustan,et al.  Metabolic activation of N-hydroxy-2-aminofluorene and N-hydroxy-2-acetylaminofluorene by monomorphic N-acetyltransferase (NAT1) and polymorphic N-acetyltransferase (NAT2) in colon cytosols of Syrian hamsters congenic at the NAT2 locus. , 1993, Cancer research.

[116]  A. Risch,et al.  Genotyping human polymorphic arylamine N-acetyltransferase: identification of new slow allotypic variants. , 1992, Pharmacogenetics.

[117]  T. Deguchi,et al.  Sequences and expression of alleles of polymorphic arylamine N-acetyltransferase of human liver. , 1992, The Journal of biological chemistry.

[118]  R. Minchin,et al.  N-and O-acetylation of aromatic and heterocyclic amine carcinogens by human monomorphic and polymorphic acetyltransferases expressed in COS-1 cells. , 1992, Biochemical and biophysical research communications.

[119]  D. Grant,et al.  Site-directed mutagenesis of recombinant human arylamine N-acetyltransferase expressed in Escherichia coli. Evidence for direct involvement of Cys68 in the catalytic mechanism of polymorphic human NAT2. , 1992, The Journal of biological chemistry.

[120]  W. Weber,et al.  2-Aminofluorene-DNA adducts in mouse urinary bladder: effect of age, sex and acetylator phenotype. , 1992, Carcinogenesis.

[121]  T. Rustan,et al.  Polymorphic and monomorphic expression of arylamine carcinogen N-acetyltransferase isozymes in tumor target organ cytosols of Syrian hamsters congenic at the polymorphic acetyltransferase locus. , 1991, The Journal of pharmacology and experimental therapeutics.

[122]  M. Butler,et al.  Metabolic activation of carcinogenic heterocyclic aromatic amines by human liver and colon. , 1991, Carcinogenesis.

[123]  S. Manabe,et al.  Detection of a carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), in cigarette smoke condensate. , 1991, Carcinogenesis.

[124]  E. Sim,et al.  N-acetyltransferase polymorphism. Comparison of phenotype and genotype in humans. , 1991, Biochemical pharmacology.

[125]  R. Minchin,et al.  Distribution of acetyltransferase activities in the intestines of rapid and slow acetylator rabbits. , 1991, Carcinogenesis.

[126]  W. Weber,et al.  Diverse point mutations in the human gene for polymorphic N-acetyltransferase. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[127]  T. Rustan,et al.  Extrahepatic expression of the N-acetylation polymorphism toward arylamine carcinogens in tumor target organs of an inbred rat model. , 1991, The Journal of pharmacology and experimental therapeutics.

[128]  T. Deguchi,et al.  Structure and restriction fragment length polymorphism of genes for human liver arylamine N-acetyltransferases. , 1991, Biochemical and biophysical research communications.

[129]  D. Grant,et al.  Molecular mechanism of slow acetylation of drugs and carcinogens in humans. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[130]  M. Díaz‐Rubio,et al.  Acetylator polymorphism in human colorectal carcinoma. , 1991, Cancer research.

[131]  D. Grant,et al.  Monomorphic and polymorphic human arylamine N-acetyltransferases: a comparison of liver isozymes and expressed products of two cloned genes. , 1991, Molecular pharmacology.

[132]  D. Hein,et al.  Acetylator genotype-dependent expression of arylamine N-acetyltransferase in human colon cytosol from non-cancer and colorectal cancer patients. , 1991, Cancer research.

[133]  T. Rustan,et al.  Purification of hepatic polymorphic arylamine N-acetyltransferase from homozygous rapid acetylator inbred hamster: identity with polymorphic N-hydroxyarylamine-O-acetyltransferase. , 1990, Cancer research.

[134]  O. Ilhan,et al.  Polymorphic N‐acetylation capacity in breast cancer patients , 1990, International journal of cancer.

[135]  R. Kato,et al.  Monomorphic and polymorphic isozymes of arylamine N-acetyltransferases in hamster liver: purification of the isozymes and genetic basis of N-acetylation polymorphism. , 1990, Carcinogenesis.

[136]  K. Ilett,et al.  Acetylation phenotype is not associated with breast cancer. , 1990, Cancer research.

[137]  D. Hein,et al.  Acetylator genotype-dependent expression of arylamine N-acetyltransferase and N-hydroxyarylamine O-acetyltransferase in Syrian inbred hamster intestine and colon. Identity with the hepatic acetylation polymorphism. , 1990, Drug metabolism and disposition: the biological fate of chemicals.

[138]  D. Grant,et al.  Human arylamine N-acetyltransferase genes: isolation, chromosomal localization, and functional expression. , 1990, DNA and cell biology.

[139]  T. Deguchi,et al.  Cloning and expression of cDNAs for polymorphic and monomorphic arylamine N-acetyltransferases from human liver. , 1990, The Journal of biological chemistry.

[140]  D. Grant,et al.  Acetylation pharmacogenetics. The slow acetylator phenotype is caused by decreased or absent arylamine N-acetyltransferase in human liver. , 1990, The Journal of clinical investigation.

[141]  D. Grant,et al.  N-acetylation pharmacogenetics: a gene deletion causes absence of arylamine N-acetyltransferase in liver of slow acetylator rabbits. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[142]  M. Reidenberg,et al.  Potential artifacts in the use of caffeine to determine acetylation phenotype. , 1989, British journal of clinical pharmacology.

[143]  P. Routledge,et al.  Drug acetylation in breast cancer. , 1989, British Journal of Cancer.

[144]  D. Grant,et al.  Nucleotide sequence of an intronless gene for a human arylamine N-acetyltransferase related to polymorphic drug acetylation. , 1989, Nucleic acids research.

[145]  D. Hein.  Acetylator genotype and arylamine-induced carcinogenesis. , 1988, Biochimica et biophysica acta.

[146]  P. Philip,et al.  Polymorphic N-acetylation capacity in lung cancer. , 1988, Carcinogenesis.

[147]  D. Hein,et al.  Acetylator genotype-dependent metabolic activation of carcinogenic N-hydroxyarylamines by S-acetyl coenzyme A-dependent enzymes of inbred hamster tissue cytosols: relationship to arylamine N-acetyltransferase. , 1987, Carcinogenesis.

[148]  P. Philip,et al.  Acetylator status and its relationship to breast cancer and other diseases of the breast. , 1987, European journal of cancer & clinical oncology.

[149]  D. Hein,et al.  Inheritance of acetylator genotype-dependent arylamine N-acetyltransferase in hamster bladder cytosol. , 1987, Carcinogenesis.

[150]  K. Ilett,et al.  Acetylation phenotype in colorectal carcinoma. , 1987, Cancer research.

[151]  F. Kadlubar,et al.  Role of aromatic amine acetyltransferase in human colorectal cancer. , 1986, Archives of surgery.

[152]  T. Smith,et al.  N-acetyltransferase multiplicity and the bioactivation of N-arylhydroxamic acids by hamster hepatic and intestinal enzymes. , 1986, Carcinogenesis.

[153]  W. Weber,et al.  Biochemical investigation of the basis for the genetic N-acetylation polymorphism in the inbred hamster. , 1985, The Journal of pharmacology and experimental therapeutics.

[154]  J. Trafford,et al.  Acetylator phenotype in patients with lung carcinoma--a negative report. , 1985, European journal of respiratory diseases.

[155]  W. Weber,et al.  N-acetylation pharmacogenetics. , 1985, Pharmacological reviews.

[156]  D. Grant,et al.  A simple test for acetylator phenotype using caffeine. , 1984, British journal of clinical pharmacology.

[157]  R. Glashan,et al.  ROLE OF N-ACETYLTRANSFERASE PHENOTYPES IN BLADDER CARCINOGENESIS: A PHARMACOGENETIC EPIDEMIOLOGICAL APPROACH TO BLADDER CANCER , 1982, The Lancet.

[158]  D. Hoffmann,et al.  Chemical Studies on Tobacco Smoke LXIV. On the Analysis of Aromatic Amines in Cigarette Smoke , 1979 .

[159]  H. Wolf,et al.  N-Acetyltransferase phenotype and risk in urinary bladder cancer: approaches in molecular epidemiology. Preliminary results in Sweden and Denmark , 1979, Environmental health perspectives.

[160]  J. W. Jennne.  Partial purification and properties of the isoniazid transacetylase in human liver. Its relationship to the acetylation of p-aminosalicylic acid. , 1965, The Journal of clinical investigation.

[161]  D. Evans,et al.  HUMAN ACETYLATION POLYMORPHISM. , 1964, The Journal of laboratory and clinical medicine.

[162]  M. Leppert,et al.  Meat consumption, genetic susceptibility, and colon cancer risk: a United States multicenter case-control study. , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[163]  M. Spitz,et al.  Polymorphisms in the N acetyltransferase 1 NAT1 gene and lung cancer risk in a minority population. , 1998, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[164]  M. Lechner,et al.  Increased frequency of wild-type arylamine-N-acetyltransferase allele NAT2*4 homozygotes in Portuguese patients with colorectal cancer. , 1998, Carcinogenesis.

[165]  W. Weber,et al.  Characterization of a hormone response element in the mouse N-acetyltransferase 2 (Nat2*) promoter. , 1998, Gene expression.

[166]  P. Dayer,et al.  N-acetyltransferase NAT1 and NAT2 genotypes and lung cancer risk. , 1998, Pharmacogenetics.

[167]  U. Meyer,et al.  Molecular mechanisms of genetic polymorphisms of drug metabolism. , 1997, Annual review of pharmacology and toxicology.

[168]  N. Probst-Hensch,et al.  Lack of association between the polyadenylation polymorphism in the NAT1 (acetyltransferase 1) gene and colorectal adenomas. , 1996, Carcinogenesis.

[169]  K T Bogen,et al.  Cancer risk of heterocyclic amines in cooked foods: an analysis and implications for research. , 1995, Carcinogenesis.

[170]  T. Rustan,et al.  Construction of Syrian hamster lines congenic at the polymorphic acetyltransferase locus (NAT2): acetylator genotype-dependent N- and O-acetylation of arylamine carcinogens. , 1994, Toxicology and applied pharmacology.

[171]  I. Roots,et al.  Debrisoquine hydroxylation phenotype, acetylation phenotype, and ABO blood groups as genetic host factors of lung cancer risk. , 1988, Klinische Wochenschrift.

[172]  W. Weber.  The acetylator genes and drug response , 1987 .

[173]  C. Jara,et al.  Hepatic acetylator polymorphism in breast cancer patients. , 1987, Oncology.

[174]  J. Pilch,et al.  N-acetyltransferase phenotype of patients with cancer of the larynx. , 1987, Neoplasma.

[175]  W. Weber,et al.  Clinical Pharmacokinetics of Isoniazid , 1979, Clinical pharmacokinetics.

[176]  M. Pavlova,et al.  Acetylator phenotype in patients with breast cancer. , 1978, Oncology.

[177]  L. H. Schmidt,et al.  Metabolism of isoniazid in man as related to the occurrence of peripheral neuritis. , 1954, American review of tuberculosis.