D W Hein

Summary

Affiliation: University of Louisville
Country: USA

Publications

  1. ncbi Association between manganese superoxide dismutase promoter gene polymorphism and breast cancer survival
    Robert C G Martin
    Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky, USA
    Breast Cancer Res 8:R45. 2006
  2. ncbi Prostate expression of N-acetyltransferase 1 (NAT1) and 2 (NAT2) in rapid and slow acetylator congenic Syrian hamster
    David W Hein
    Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, University of Louisville School of Medicine, Kentucky 40292, USA
    Pharmacogenetics 13:159-67. 2003
  3. ncbi Systemic functional expression of N-acetyltransferase polymorphism in the F344 Nat2 congenic rat
    David W Hein
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA
    Drug Metab Dispos 36:2452-9. 2008
  4. ncbi Changes in consensus arylamine N-acetyltransferase gene nomenclature
    David W Hein
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky, USA
    Pharmacogenet Genomics 18:367-8. 2008
  5. ncbi Phenotype of the most common "slow acetylator" arylamine N-acetyltransferase 1 genetic variant (NAT1*14B) is substrate-dependent
    Lori M Millner
    Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA
    Drug Metab Dispos 40:198-204. 2012
  6. ncbi Molecular genetics and function of NAT1 and NAT2: role in aromatic amine metabolism and carcinogenesis
    David W Hein
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA
    Mutat Res 506:65-77. 2002
  7. ncbi Association of prostate cancer with rapid N-acetyltransferase 1 (NAT1*10) in combination with slow N-acetyltransferase 2 acetylator genotypes in a pilot case-control study
    David W Hein
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
    Environ Mol Mutagen 40:161-7. 2002
  8. ncbi N-acetyltransferase (Nat) 1 and 2 expression in Nat2 knockout mice
    Jennifer A Loehle
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA
    J Pharmacol Exp Ther 319:724-8. 2006
  9. ncbi Effects of single nucleotide polymorphisms in human N-acetyltransferase 2 on metabolic activation (O-acetylation) of heterocyclic amine carcinogens
    David W Hein
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, KY 40292, USA
    Int J Cancer 119:1208-11. 2006
  10. ncbi N-acetyltransferase 2 genetic polymorphism: effects of carcinogen and haplotype on urinary bladder cancer risk
    D W Hein
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA
    Oncogene 25:1649-58. 2006

Research Grants

  1. UofL Environmental Health Sciences Training Program
    David Hein; Fiscal Year: 2007
  2. PHARMACOGENETICS OF DRUG AND CARCINOGEN METABOLISM
    David Hein; Fiscal Year: 2007
  3. PHARMACOGENETICS OF DRUG AND CARCINOGEN METABOLISM
    David Hein; Fiscal Year: 2001
  4. PHARMACOGENETICS OF DRUG AND CARCINOGEN METABOLISM
    David Hein; Fiscal Year: 2009

Detail Information

Publications94

  1. ncbi Association between manganese superoxide dismutase promoter gene polymorphism and breast cancer survival
    Robert C G Martin
    Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky, USA
    Breast Cancer Res 8:R45. 2006
    ..The aim of our study was to investigate possible associations of the -102 C>T polymorphism with overall and relapse-free breast cancer survival in a hospital-based case-only study...
  2. ncbi Prostate expression of N-acetyltransferase 1 (NAT1) and 2 (NAT2) in rapid and slow acetylator congenic Syrian hamster
    David W Hein
    Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, University of Louisville School of Medicine, Kentucky 40292, USA
    Pharmacogenetics 13:159-67. 2003
    ..The results provide mechanistic support for a role of NAT1 and/or NAT2 acetylator polymorphism(s) in human prostate cancer risk related to aromatic and/or heterocyclic amine carcinogens...
  3. ncbi Systemic functional expression of N-acetyltransferase polymorphism in the F344 Nat2 congenic rat
    David W Hein
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA
    Drug Metab Dispos 36:2452-9. 2008
    ..These congenic rat lines are useful for investigating the role of NAT2 genetic polymorphisms in susceptibility to cancers related to arylamine carcinogen exposures...
  4. ncbi Changes in consensus arylamine N-acetyltransferase gene nomenclature
    David W Hein
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky, USA
    Pharmacogenet Genomics 18:367-8. 2008
    ..louisville.edu. New NAT alleles should continue to be submitted to the NAT Nomenclature Committee for inclusion on the website to ensure proper categorization and to continue consistency in nomenclature...
  5. ncbi Phenotype of the most common "slow acetylator" arylamine N-acetyltransferase 1 genetic variant (NAT1*14B) is substrate-dependent
    Lori M Millner
    Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA
    Drug Metab Dispos 40:198-204. 2012
    ..NAT1 14B-catalyzed acetylation phenotype is substrate-dependent, and NAT1 14B exhibits higher N- and O-acetylation catalytic efficiency as well as DNA adducts after exposure to the human carcinogen 4-aminobiphenyl...
  6. ncbi Molecular genetics and function of NAT1 and NAT2: role in aromatic amine metabolism and carcinogenesis
    David W Hein
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA
    Mutat Res 506:65-77. 2002
    ..Human NAT1 and NAT2 alleles have been characterized by recombinant expression to further understand the effects of nucleotide polymorphisms on function and phenotype...
  7. ncbi Association of prostate cancer with rapid N-acetyltransferase 1 (NAT1*10) in combination with slow N-acetyltransferase 2 acetylator genotypes in a pilot case-control study
    David W Hein
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
    Environ Mol Mutagen 40:161-7. 2002
    ..This finding should be investigated further in larger cohorts and in other ethnic populations...
  8. ncbi N-acetyltransferase (Nat) 1 and 2 expression in Nat2 knockout mice
    Jennifer A Loehle
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA
    J Pharmacol Exp Ther 319:724-8. 2006
    ..The Nat2 KO model will be useful in future studies to assess the role of Nat2 in arylamine carcinogenesis...
  9. ncbi Effects of single nucleotide polymorphisms in human N-acetyltransferase 2 on metabolic activation (O-acetylation) of heterocyclic amine carcinogens
    David W Hein
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, KY 40292, USA
    Int J Cancer 119:1208-11. 2006
    ..05) decreased catalytic activity towards the O-acetylation of N--OH--MeIQx but not N--OH--PhIP. These results have important implications towards the interpretation of molecular epidemiological studies of NAT2 genotype and cancer risk...
  10. ncbi N-acetyltransferase 2 genetic polymorphism: effects of carcinogen and haplotype on urinary bladder cancer risk
    D W Hein
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA
    Oncogene 25:1649-58. 2006
    ....
  11. ncbi Molecular genetics and epidemiology of the NAT1 and NAT2 acetylation polymorphisms
    D W Hein
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Kentucky 40292, USA
    Cancer Epidemiol Biomarkers Prev 9:29-42. 2000
    ....
  12. ncbi N-acetyltransferase SNPs: emerging concepts serve as a paradigm for understanding complexities of personalized medicine
    David W Hein
    University of Louisville School of Medicine, James Graham Brown Cancer Center, Center for Environmental Genomics and Integrative Biology, Department of Pharmacology and Toxicology, Louisville, KY 40292, USA
    Expert Opin Drug Metab Toxicol 5:353-66. 2009
    ..As medical care moves to a more personalized approach, the implications of these confounding factors will be important in understanding the complexities of personalized medicine...
  13. ncbi Pharmacogenetics of the arylamine N-acetyltransferases: a symposium in honor of Wendell W. Weber
    D W Hein
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky, USA
    Drug Metab Dispos 28:1425-32. 2000
    ..The symposium honored Wendell W. Weber for over 35 years of leadership and scientific advancement in pharmacogenetics and was highlighted by his overview of the historical development of the field...
  14. ncbi N-Acetyltransferase genetics and their role in predisposition to aromatic and heterocyclic amine-induced carcinogenesis
    D W Hein
    Department of Pharmacology, University of Louisville School of Medicine, Louisville, KY, USA
    Toxicol Lett 112:349-56. 2000
    ..These findings may relate to variability in carcinogen exposures and to differences in acetylator genotype/phenotype determinations...
  15. ncbi DNA adduct levels and absence of tumors in female rapid and slow acetylator congenic hamsters administered the rat mammary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine
    A J Fretland
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, KY 40292, USA
    J Biochem Mol Toxicol 15:26-33. 2001
    ..Unlike the rat, PhIP did not induce breast or any other tumors in female rapid and slow acetylator congenic hamsters administered high-dose PhIP (10 doses of 75 mg/kg) and a high-fat diet...
  16. ncbi N-Acetyltransferase-2 genetic polymorphism, well-done meat intake, and breast cancer risk among postmenopausal women
    A C Deitz
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Kentucky 40292, USA
    Cancer Epidemiol Biomarkers Prev 9:905-10. 2000
    ....
  17. ncbi Oral administration of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) yields PhIP-DNA adducts but not tumors in male Syrian hamsters congenic at the N-acetyltransferase 2 (NAT2) locus
    A J Fretland
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
    Toxicol Sci 59:226-30. 2001
    ..However, no tumors were observed in male rapid and slow acetylator congenic hamsters administered 11 oral doses of PhIP (75 mg/kg) and maintained on a high fat diet for one year...
  18. ncbi Functional characterization of nucleotide polymorphisms in the coding region of N-acetyltransferase 1
    A J Fretland
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky, USA
    Pharmacogenetics 11:511-20. 2001
    ..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...
  19. ncbi Rodent models of the human acetylation polymorphism: comparisons of recombinant acetyltransferases
    D W Hein
    Department of Pharmacology and Toxicology, University of North Dakota School of Medicine and Health Sciences, Grand Forks 58202 9037, USA
    Mutat Res 376:101-6. 1997
    ..The acetylation polymorphisms in mouse, Syrian hamster, and rat are herein reviewed and compared as models of the human acetylation polymorphism...
  20. ncbi Nomenclature for N-acetyltransferases
    K P Vatsis
    Department of Pharmacology, Medical School, University of Michigan, Ann Arbor 48109 0632, USA
    Pharmacogenetics 5:1-17. 1995
    ..For designation of genotypes at a single NAT* locus, a slash serves to separate the alleles; in phenotype designations, which are not italicized, alleles are separated by a comma...
  21. ncbi Identification of a novel allele at the human NAT1 acetyltransferase locus
    M A Doll
    Department of Pharmacology and Toxicology, University of North Dakota School of Medicine and Health Sciences, Grand Forks 58202 9037, USA
    Biochem Biophys Res Commun 233:584-91. 1997
    ....
  22. ncbi 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
    A J Fretland
    Department of Pharmacology and Toxicology, University of North Dakota School of Medicine and Health Sciences, Grand Forks 58202 9037, USA
    Toxicol Appl Pharmacol 142:360-6. 1997
    ..These studies demonstrate metabolic activation and deactivation by recombinant mouse NAT1, NAT2, and NAT3 proteins and confirm and extend previous studies on the molecular basis for the acetylation polymorphism in the mouse...
  23. ncbi Effect of nucleotide substitutions in N-acetyltransferase-1 on N-acetylation (deactivation) and O-acetylation (activation) of arylamine carcinogens: implications for cancer predisposition
    Adrian J Fretland
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, KY 40292, USA
    Cancer Detect Prev 26:10-4. 2002
    ..These results show an important effect of the NAT1 genetic polymorphism on the N- and O-acetylation of arylamine carcinogens, suggesting modification of cancer susceptibility following exposures to arylamine carcinogens...
  24. ncbi Effect of N-acetyltransferase 2 polymorphism on tumor target tissue DNA adduct levels in rapid and slow acetylator congenic rats administered 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine or 2-amino-3,8-dimethylimidazo-[4,5-f]quinoxaline
    Kristin J Metry
    Department of Pharmacology and Toxicology, James Graham Brown Cancer Center and Center for Environmental Genomics and Integrative Biology, University of Louisville School of Medicine, Louisville, Kentucky, USA
    Drug Metab Dispos 37:2123-6. 2009
    ..001) higher in rapid acetylator liver than in slow acetylator liver. Our results are consistent with the tumor target specificity of PhIP and MeIQx and with increased susceptibility to MeIQx-induced liver tumors in rapid NAT2 acetylators...
  25. ncbi Metabolic activation of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine in Syrian hamsters congenic at the N-acetyltransferase 2 (NAT2) locus
    Adrian J Fretland
    Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
    Toxicol Sci 74:253-9. 2003
    ..DNA-adduct levels following administration of PhIP or N-hydroxy-PhIP did not correlate with either N-hydroxy-PhIP O-acetyltransferase or O-sulfotransferase catalytic activities...
  26. ncbi Functional characterization of human N-acetyltransferase 2 (NAT2) single nucleotide polymorphisms
    A J Fretland
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA
    Pharmacogenetics 11:207-15. 2001
    ..These results suggest two mechanisms for slow acetylator phenotype(s) and more clearly define the effects of individual SNPs on human NAT2 expression, stability and catalytic activity...
  27. ncbi 4-Aminobiphenyl downregulation of NAT2 acetylator genotype-dependent N- and O-acetylation of aromatic and heterocyclic amine carcinogens in primary mammary epithelial cell cultures from rapid and slow acetylator rats
    Felicia A Jefferson
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
    Toxicol Sci 107:293-7. 2009
    ..These studies clearly show NAT2 acetylator genotype-dependent N- and O-acetylation of aromatic and heterocyclic amine carcinogens in rat mammary epithelial cell cultures to be subject to downregulation by the arylamine carcinogen ABP...
  28. ncbi Role of human CYP1A1 and NAT2 in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced mutagenicity and DNA adducts
    J Bendaly
    Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, and Center for Environmental Genomics and Integrative Biology, University of Louisville School of Medicine, Louisville, KY, USA
    Xenobiotica 39:399-406. 2009
    ..05) following one-way analysis of variance. These results strongly support activation of PhIP by CYP1A1 with little effect of human NAT2 genetic polymorphism on mutagenesis and DNA damage...
  29. ncbi Functional effects of single nucleotide polymorphisms in the coding region of human N-acetyltransferase 1
    Y Zhu
    Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40292, USA
    Pharmacogenomics J 8:339-48. 2008
    ..These results suggest heterogeneity among slow NAT1 acetylator phenotypes...
  30. ncbi Codominant expression of N-acetylation and O-acetylation activities catalyzed by N-acetyltransferase 2 in human hepatocytes
    Mark A Doll
    Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky 40202 1617, USA
    J Pharmacol Exp Ther 334:540-4. 2010
    ....
  31. ncbi An alternative cyclin-D1 splice site is not linked to inflammatory bowel disease-associated neoplasia
    Ziad Kanaan
    Price Institute of Surgical Research, Department of Surgery, University of Louisville School of Medicine, Louisville, KY USA
    Int J Biol Markers 25:27-31. 2010
    ..This creates a higher concentration of CCND1, facilitating easier passage through the G1/S checkpoint, abnormal cell cycle progression, and possibly carcinogenesis...
  32. ncbi Quantitative tissue and gene-specific differences and developmental changes in Nat1, Nat2, and Nat3 mRNA expression in the rat
    David F Barker
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA
    Drug Metab Dispos 36:2445-51. 2008
    ....
  33. ncbi N-acetyltransferase 2 genotype modification of active cigarette smoking on breast cancer risk among hispanic and non-hispanic white women
    Kathy B Baumgartner
    Department of Epidemiology and Population Health, University of Louisville, Louisville, Kentucky 40292, USA
    Toxicol Sci 112:211-20. 2009
    ..29; 95% CI, 1.16-4.51). Results for Hispanic women were not statistically significant. These findings support smoking as a risk factor for breast cancer among non-Hispanic white women with very slow NAT2 acetylator phenotype...
  34. ncbi Functional properties of an alternative, tissue-specific promoter for human arylamine N-acetyltransferase 1
    David F Barker
    Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40292, USA
    Pharmacogenet Genomics 16:515-25. 2006
    ..These findings imply a fundamental role for P3 in NAT1 regulation and define additional regions for genetic polymorphisms associated with enhanced cancer risk...
  35. ncbi 4,4'-methylenedianiline-induced hepatotoxicity is modified by N-acetyltransferase 2 (NAT2) acetylator polymorphism in the rat
    Xiaoyan Zhang
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA
    J Pharmacol Exp Ther 316:289-94. 2006
    ..These results suggest that acetylator phenotype is an important factor for susceptibility toward MDA hepatotoxicity...
  36. ncbi Functional characterization of single-nucleotide polymorphisms and haplotypes of human N-acetyltransferase 2
    Yu Zang
    Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40292, USA
    Carcinogenesis 28:1665-71. 2007
    ..Our results suggest that coding region SNPs confer slow acetylator phenotype by multiple mechanisms that also may vary with arylamine exposures...
  37. ncbi Cloning, sequencing and expression of NAT1 and NAT2 encoding genes from rapid and slow acetylator inbred rats
    M A Doll
    Department of Pharmacology and Toxicology, University of North Dakota School of Medicine, Grand Forks 58202-9037, USA
    Pharmacogenetics 5:247-51. 1995
  38. ncbi Functional characterization of the A411T (L137F) and G364A (D122N) genetic polymorphisms in human N-acetyltransferase 2
    Yu Zang
    Department of Pharmacology and Toxicology, Center for Genetics and Molecular Medicine and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
    Pharmacogenet Genomics 17:37-45. 2007
    ..We undertook a study to characterize these new single nucleotide polymorphisms and NAT2 alleles to further our understanding of genotype/phenotype relationships in human populations...
  39. ncbi Functional analysis of the human N-acetyltransferase 1 major promoter: quantitation of tissue expression and identification of critical sequence elements
    Anwar Husain
    Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40292, USA
    Drug Metab Dispos 35:1649-56. 2007
    ..The 200L29 EMSA shift could not be competed by consensus Sp1 or AP-2 oligonucleotides, and may represent binding of a transcription factor that is common to N-acetyltransferase genes in humans and other species...
  40. ncbi Simultaneous determination of 7 N-acetyltransferase-2 single-nucleotide variations by allele-specific primer extension assay
    Yusheng Zhu
    Department of Pathology and Laboratory Medicine, University of Louisville School of Medicine, Louisville, KY 40202, USA
    Clin Chem 52:1033-9. 2006
    ..Genotyping of N-acetyltransferase-2 (NAT2) is useful in predicting the risk for toxicity of NAT2 substrates. Current methods cannot detect the 7 most important single-nucleotide variations in NAT2 simultaneously in 1 tube...
  41. ncbi 2-Amino-3,8-dimethylimidazo-[4,5-f]quinoxaline-induced DNA adduct formation and mutagenesis in DNA repair-deficient Chinese hamster ovary cells expressing human cytochrome P4501A1 and rapid or slow acetylator N-acetyltransferase 2
    Jean Bendaly
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA
    Cancer Epidemiol Biomarkers Prev 16:1503-9. 2007
    ..The results provide laboratory-based support for epidemiologic studies reporting higher frequency of heterocyclic amine-related cancers in rapid NAT2 acetylators...
  42. ncbi Structure/function evaluations of single nucleotide polymorphisms in human N-acetyltransferase 2
    Jason M Walraven
    Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
    Curr Drug Metab 9:471-86. 2008
    ..This analysis advances understanding of NAT2 structure-function relationships, important for interpreting the role of NAT2 genetic polymorphisms in bioactivation and detoxification of arylamine and hydrazine drugs and carcinogens...
  43. ncbi Tissue distribution of N-acetyltransferase 1 and 2 catalyzing the N-acetylation of 4-aminobiphenyl and O-acetylation of N-hydroxy-4-aminobiphenyl in the congenic rapid and slow acetylator Syrian hamster
    David W Hein
    Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, The University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
    Mol Carcinog 45:230-8. 2006
    ..These conclusions are important for interpretation of molecular epidemiological investigations into the role of N-acetyltransferase polymorphisms in various diseases including cancer...
  44. ncbi Identification of the major promoter and non-coding exons of the human arylamine N-acetyltransferase 1 gene (NAT1)
    Anwar Husain
    Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, Kentucky, USA
    Pharmacogenetics 14:397-406. 2004
    ..8 kb upstream of the translated exon, and the mature spliced mRNA includes at least one additional non-coding exon...
  45. ncbi Rapid genotype method to distinguish frequent and/or functional polymorphisms in human N-acetyltransferase-1
    Mark A Doll
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
    Anal Biochem 301:328-32. 2002
  46. ncbi Tissue expression and genomic sequences of rat N-acetyltransferases rNat1, rNat2, rNat3, and Functional characterization of a novel rNat3*2 genetic variant
    Jason M Walraven
    Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
    Toxicol Sci 99:413-21. 2007
    ..This study concludes that rNat1 and rNat2 are primarily responsible for acetylation phenotype in rats...
  47. ncbi Manganese superoxide dismutase V16A single-nucleotide polymorphism in the mitochondrial targeting sequence is associated with reduced enzymatic activity in cryopreserved human hepatocytes
    Robert C G Martin
    Division of Surgical Oncology, Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky, USA
    DNA Cell Biol 28:3-7. 2009
    ..05). The -9 T>C (V16A) polymorphism in the MnSOD mitochondrial targeting sequence significantly reduced MnSOD catalytic activity in cryopreserved hepatocytes, consistent with its reported associations with cancer risk and treatment...
  48. ncbi Association of the histamine N-methyltransferase C314T (Thr105Ile) polymorphism with atopic dermatitis in Caucasian children
    Mary Jayne Kennedy
    Kosair Charities Pediatric Clinical Research Unit, Department of Pediatrics, School of Medicine, University of Louisville, Louisville, KY 40202, USA
    Pharmacotherapy 28:1495-501. 2008
    ..To investigate potential associations between the histamine N-methyltransferase (HNMT) gene, HNMT, C314T (Thr105Ile) polymorphism and atopic dermatitis in a cohort of Caucasian children...
  49. ncbi The T341C (Ile114Thr) polymorphism of N-acetyltransferase 2 yields slow acetylator phenotype by enhanced protein degradation
    Yu Zang
    Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, and Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY, USA
    Pharmacogenetics 14:717-23. 2004
    ..CONCLUSION: This is the first report indicating that protein degradation is an important mechanism of human NAT2 slow acetylator phenotype...
  50. ncbi Method for determination of (-102C>T) single nucleotide polymorphism in the human manganese superoxide dismutase promoter
    Robert C G Martin
    Department of Surgery, University of Louisville School of Medicine, Louisville, KY, USA
    BMC Genet 5:33. 2004
    ..The aim of our study was to develop a method to identify and determine the frequency of this (-102C>T) polymorphism in human tissues...
  51. ncbi Identification of N-acetyltransferase 2 (NAT2) transcription start sites and quantitation of NAT2-specific mRNA in human tissues
    Anwar Husain
    Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40292, USA
    Drug Metab Dispos 35:721-7. 2007
    ..NAT2 expression in diverse human tissues provides further mechanistic support underlying associations between NAT2 genetic polymorphism, drug toxicity, and/or chemical carcinogenesis...
  52. ncbi Lack of association of the N-acetyltransferase NAT1*10 allele with prostate cancer incidence, grade, or stage among smokers in Finland
    LaCreis R Kidd
    Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville Health Sciences Center, 505 S Hancock St, Louisville, KY 40292, USA
    Biochem Genet 49:73-82. 2011
    ..28; 95% CI, 0.66-2.47), aggressive disease (OR = 0.58; 95% CI, 0.13-2.67), or advanced disease (OR = 1.19; 95% CI, 0.49-2.91)...
  53. ncbi Manganese superoxide dismutase expression as a function of genotype and lung cancer pathology
    Robert C G Martin
    Department of Surgery, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky, USA
    Cancer Invest 28:813-9. 2010
    ..The aim of this study was to compare the manganese superoxide dismutase (MnSOD) expression in matched tumor and normal tissue...
  54. ncbi Characterization of N-acetyltransferase 1 and 2 polymorphisms and haplotype analysis for inflammatory bowel disease and sporadic colorectal carcinoma
    Suhal S Mahid
    Price Institute of Surgical Research, Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292, USA
    BMC Med Genet 8:28. 2007
    ..We hypothesized that NAT1 and/or NAT2 polymorphisms contribute to the increased cancer evident in IBD...
  55. ncbi Manganese superoxide dismutase gene coding region polymorphisms lack clinical incidence in general population
    Robert C G Martin
    Department of Surgery, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY, USA
    DNA Cell Biol 27:321-3. 2008
    ..This study suggests that although the 58T > C and 60C > T polymorphisms reduce MnSOD enzymatic activity, these polymorphisms were not identified in the present case-control study population...
  56. ncbi Structure-function analyses of single nucleotide polymorphisms in human N-acetyltransferase 1
    Jason M Walraven
    Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky 40292, USA
    Drug Metab Rev 40:169-84. 2008
    ..The analysis enhances knowledge of NAT1 structure-function relationships, important for understanding associations of NAT1 SNPs with genetic predisposition to cancer, birth defects, and other diseases...
  57. ncbi Identification and characterization of functional rat arylamine N-acetyltransferase 3: comparisons with rat arylamine N-acetyltransferases 1 and 2
    Jason M Walraven
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA
    J Pharmacol Exp Ther 319:369-75. 2006
    ..This study is the first to report a third arylamine N-acetyltransferase isozyme with significant functional capacity...
  58. ncbi No apparent association between genetic polymorphisms (-102 C>T) and (-9 T>C) in the human manganese superoxide dismutase gene and gastric cancer(1)
    Robert C G Martin
    Department of Surgery, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA
    J Surg Res 124:92-7. 2005
    ..The aim of our study was to investigate possible associations of the (-9 T>C) and (-102 C>T) polymorphisms with gastric cancer in a population-based case-control study conducted in Warsaw, Poland...
  59. ncbi Examination of polymorphic glutathione S-transferase (GST) genes, tobacco smoking and prostate cancer risk among men of African descent: a case-control study
    Nicole A Lavender
    Department of Pharmacology and Toxicology, University of Louisville UofL, School of Medicine, 500 South Preston Street, Room 1319 Research Tower, UofL Health Science Center, Louisville, KY 40202, USA
    BMC Cancer 9:397. 2009
    ..Thus, we evaluated the effects of polymorphic GSTs (M1, T1, and P1) alone and combined with cigarette smoking on PCA susceptibility...
  60. ncbi Symposium overview: the role of genetic polymorphism and repair deficiencies in environmental disease
    J E Hulla
    Department of Pharmacology and Toxicology, University of North Dakota School of Medicine, Grand Forks 58202, USA
    Toxicol Sci 47:135-43. 1999
    ....
  61. ncbi Differences between human slow N-acetyltransferase 2 alleles in levels of 4-aminobiphenyl-induced DNA adducts and mutations
    Jean Bendaly
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, United States
    Mutat Res 671:13-9. 2009
    ....
  62. ncbi 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine-induced DNA adducts and genotoxicity in chinese hamster ovary (CHO) cells expressing human CYP1A2 and rapid or slow acetylator N-acetyltransferase 2
    Kristin J Metry
    Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40292, USA
    Mol Carcinog 46:553-63. 2007
    ..These results strongly support an activation role for CYP1A2 in PhIP-induced mutagenesis and DNA damage and suggest a modest effect of human NAT2 and its genetic polymorphism on PhIP DNA adduct levels...
  63. ncbi Genetic profiling of colon cancer
    Holly L Neibergs
    Norton Hereditary Cancer Institute, Louisville, Kentucky, USA
    J Surg Oncol 80:204-13. 2002
  64. ncbi Dose-dependent reduction of 3,2'-dimethyl-4-aminobiphenyl-derived DNA adducts in colon and liver of rats administered celecoxib
    Srivani Ravoori
    James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, United States
    Mutat Res 638:103-9. 2008
    ..The reduction in DMABP-DNA adduct levels in celecoxib-treated animals provides further support for celecoxib as a chemopreventive agent for colorectal cancer...
  65. ncbi Functional genomics of C190T single nucleotide polymorphism in human N-acetyltransferase 2
    Yuanqi Zhu
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, KY 40292, USA
    Biol Chem 383:983-7. 2002
    ..These results show that NAT2*19 possessing the C190T (R64W) SNP encodes a slow acetylator phenotype for both N- and O-acetylation, due to a reduction in the amount and stability of the NAT2 19 allozyme...
  66. ncbi Chemoprevention of arylamine-induced colorectal aberrant crypts
    Yi Feng
    Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40292, USA
    Exp Biol Med (Maywood) 233:71-5. 2008
    ..05). Reductions in both AC and ACF were highest following treatment with 1000 ppm celecoxib. These results provide additional experimental support for the chemopreventive effects of COX inhibitors in arylamine-induced colorectal cancer...
  67. ncbi Effect of rapid human N-acetyltransferase 2 haplotype on DNA damage and mutagenesis induced by 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazo-[4,5-f]quinoxaline (MeIQx)
    Kristin J Metry
    Department of Pharmacology and Toxicology, James Graham Brown Cancer Center and Center for Environmental Genomics and Integrative Biology, University of Louisville School of Medicine, Louisville, KY 40292, USA
    Mutat Res 684:66-73. 2010
    ..DNA adduct levels correlated very highly with hprt mutants for both IQ and MeIQx. These results suggest substantially increased risk for IQ- and MeIQx-induced DNA damage and mutagenesis in rapid NAT2 acetylators...
  68. ncbi Inducible nitric oxide synthase is required in alcohol-induced liver injury: studies with knockout mice
    Stephen E McKim
    Department of Pharmacology, University of North Carolina, Chapel Hill, USA
    Gastroenterology 125:1834-44. 2003
    ..However, the production of the free radical nitric oxide (NO*) by inducible nitric oxide synthase (iNOS) could also be involved...
  69. ncbi Clinical pharmacogenetics in pediatric patients
    Anwar Husain
    University of Louisville, Department of Pharmacology and Toxicology and James Graham Brown Center, School of Medicine, Louisville, KY, USA
    Pharmacogenomics 8:1403-11. 2007
    ....
  70. ncbi Computational and experimental analyses of mammalian arylamine N-acetyltransferase structure and function
    Jason M Walraven
    Department of Pharmacology, University of Louisville School of Medicine, Louisville, KY 40292, USA
    Drug Metab Dispos 35:1001-7. 2007
    ..This study demonstrates both the utility and limitations of computational structural modeling with proteins that differ as much as the mammalian and bacterial NATs...
  71. ncbi Chemopreventive drug treatment in subjects with genetic predisposition to cancer: prescriber liability and healthcare disparities
    Larry I Palmer
    Institute for Bioethics, Health Policy and Law, University of Louisville, Kentucky, USA
    Pharmacogenomics 5:319-29. 2004
    ..Management of the risks related to chemopreventive treatment will differ from traditional disease management. Knowledge about cancer susceptibility will need to consider environmental factors as they relate to healthcare disparities...
  72. ncbi Role of the renin-angiotensin system in hepatic ischemia reperfusion injury in rats
    Luping Guo
    Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville Health Sciences Center, Louisville, KY 40292, USA
    Hepatology 40:583-9. 2004
    ..These data further suggest that the RAS may play a key role in mediating such responses in the liver and suggest a novel role for this system...
  73. ncbi Metallothionein suppresses angiotensin II-induced nicotinamide adenine dinucleotide phosphate oxidase activation, nitrosative stress, apoptosis, and pathological remodeling in the diabetic heart
    Guihua Zhou
    Department of Medicine, University of Louisville School of Medicine, Louisville, Kentucky, USA
    J Am Coll Cardiol 52:655-66. 2008
    ..We evaluated metallothionein (MT)-mediated cardioprotection from angiotensin II (Ang II)-induced pathologic remodeling with and without underlying diabetes...
  74. ncbi Genetic polymorphisms in heterocyclic amine metabolism and risk of colorectal adenomas
    Naoko Ishibe
    Genetic Epidemioly Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20892, USA
    Pharmacogenetics 12:145-50. 2002
    ..Further study of larger populations is needed to confirm and extend these observations...
  75. ncbi Meat intake, heterocyclic amine exposure, and metabolizing enzyme polymorphisms in relation to colorectal polyp risk
    Aesun Shin
    Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, 8th Floor, 2525 West End Avenue, Nashville, TN 37203, USA
    Cancer Epidemiol Biomarkers Prev 17:320-9. 2008
    ..These results provide strong evidence for a modifying effect of metabolizing genes on the association of meat intake and HCA exposure with colorectal polyp risk...
  76. ncbi Interaction of the cytochrome P4501A2, SULT1A1 and NAT gene polymorphisms with smoking and dietary mutagen intake in modification of the risk of pancreatic cancer
    Hideo Suzuki
    Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Carcinogenesis 29:1184-91. 2008
    ..These data suggest the existence of gender-specific susceptibility to tobacco carcinogen and dietary mutagen exposure in PC...
  77. ncbi Impact of misclassification in genotype-exposure interaction studies: example of N-acetyltransferase 2 (NAT2), smoking, and bladder cancer
    Anne C Deitz
    Center for Cancer Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, USA
    Cancer Epidemiol Biomarkers Prev 13:1543-6. 2004
    ..This example illustrates how reducing genotype misclassification can result in substantial decreases in sample size requirements and possibly substantial decreases in the cost of studies to evaluate interactions...
  78. ncbi Urinary acetylated metabolites and N-acetyltransferase-2 genotype in human subjects treated with a para-phenylenediamine-containing oxidative hair dye
    Gerhard J Nohynek
    L OREAL Research and Development, River Plaza Building, 25 29 quai Aulagnier, 92600 Asnières, France
    Food Chem Toxicol 42:1885-91. 2004
    ..9%, respectively. Overall, our results suggest that the human acetylation rate of PPD after topical application is independent of the NAT2 genotype status, most likely due to metabolism by epidermal NAT1 prior to systemic absorption...
  79. ncbi Polymorphisms of cytochrome P4501A2 and N-acetyltransferase genes, smoking, and risk of pancreatic cancer
    Donghui Li
    Department of Gastrointestinal Medical Oncology, The University of Texas, M D Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 426, Houston, TX 77030, USA
    Carcinogenesis 27:103-11. 2006
    ..9, 95% CI: 1.2-6.9) and among females (AOR: 2.5, 95% CI: 1.1-5.7). These data suggest that polymorphisms of the CYP1A2 and NAT1 genes modify the risk of pancreatic cancer...
  80. ncbi NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta-analyses
    Montserrat Garcia-Closas
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, MD 20852 7234, USA
    Lancet 366:649-59. 2005
    ..Associations between polymorphisms in other NAT and GST genes and bladder-cancer risk have been inconsistent...
  81. ncbi N-acetyltransferase (NAT1, NAT2) and glutathione S-transferase (GSTM1, GSTT1) polymorphisms in breast cancer
    Kyoung Mu Lee
    Department of Preventive Medicine, Seoul National University College of Medicine, Cancer Research Institute, 28 Yongon Dong, Chongno Gu, Seoul 110 799, South Korea
    Cancer Lett 196:179-86. 2003
    ..1, 95% CI=1.0-9.1). These results suggest that genetic polymorphisms of NAT1 and NAT2 have no independent effect on breast cancer risk, but they modulate breast cancer risk in the presence of GSTM1 and GSTT1 null genotypes...
  82. ncbi Bioactivation, protein haptenation, and toxicity of sulfamethoxazole and dapsone in normal human dermal fibroblasts
    Payal Bhaiya
    Division of Pharmaceutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, USA
    Toxicol Appl Pharmacol 215:158-67. 2006
    ..Further work is needed to determine the role of the observed toxicity in mediating CDRs observed with these agents...
  83. ncbi NAT2 slow acetylation and GSTM1 null genotypes may increase postmenopausal breast cancer risk in long-term smoking women
    Olga L van der Hel
    Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands
    Pharmacogenetics 13:399-407. 2003
    ....
  84. ncbi Genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2) and risk of non-Hodgkin lymphoma
    Lindsay M Morton
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland 20852, USA
    Pharmacogenet Genomics 16:537-45. 2006
    ..15-5.20, P = 0.02). Our data provide evidence that NAT1 and NAT2 genotypes are associated with NHL risk and support a contributory role for carcinogenic aromatic and/or heterocyclic amines in the multi-factorial etiology of NHL...
  85. ncbi No apparent association between NAT1 and NAT2 genotypes and risk of stomach cancer
    Qing Lan
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland 20892-7240, USA
    Cancer Epidemiol Biomarkers Prev 12:384-6. 2003
  86. ncbi Permanent hair dyes and bladder cancer: risk modification by cytochrome P4501A2 and N-acetyltransferases 1 and 2
    Manuela Gago-Dominguez
    USC Norris Comprehensive Cancer Center, Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033 0800, USA
    Carcinogenesis 24:483-9. 2003
    ..On the other hand, individuals of NAT1*10 genotype exhibited no such associations...
  87. ncbi Cigarette smoking, N-acetyltransferase genes and the risk of advanced colorectal adenoma
    Roxana Moslehi
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 6120 Executive Blvd, EPS 8047, Rockville, MD 20852 USA
    Pharmacogenomics 7:819-29. 2006
    ..Our interest is in the polymorphisms within the NAT1 and NAT2 genes that influence the tobacco-colorectal tumor relationship by impacting on the metabolic activation and detoxification of tobacco smoke-derived carcinogens...
  88. ncbi Commentary: Reflections on G. M. Lower and colleagues' 1979 study associating slow acetylator phenotype with urinary bladder cancer: meta-analysis, historical refinements of the hypothesis, and lessons learned
    Nathaniel Rothman
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health/DHHS, Bethesda, MD 20892, USA
    Int J Epidemiol 36:23-8. 2007
  89. ncbi Evidence for an intensity-dependent interaction of NAT2 acetylation genotype and cigarette smoking in the Spanish Bladder Cancer Study
    Jay H Lubin
    Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, Rockville, MD 20852, USA
    Int J Epidemiol 36:236-41. 2007
    ..9 in never-smokers and 1.6 in ever-smokers, a 1.8-fold enhancement in smokers. Evidence indicates that acetylation is an exposure-dependent process, and thus the magnitude of the interaction may also depend on exposure level...
  90. ncbi Hair dye use, genetic variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and risk of non-Hodgkin lymphoma
    Lindsay M Morton
    Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, MD 20852, USA
    Carcinogenesis 28:1759-64. 2007
    ..Several previous studies have found non-Hodgkin lymphoma (NHL) risk to be associated with hair dye use, particularly use of permanent, dark colors and use before 1980, when hair dye formulations changed...
  91. ncbi Association of metabolic gene polymorphisms with tobacco consumption in healthy controls
    Kim M Smits
    University Maastricht, Maastricht, The Netherlands
    Int J Cancer 110:266-70. 2004
    ..No association between polymorphisms in the genes studied and tobacco consumption was observed; therefore, no effect of these genes on smoking behavior should be expected...
  92. ncbi Haplotype of N-acetyltransferase 1 and 2 and risk of pancreatic cancer
    Li Jiao
    Department of Gastrointestinal Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Cancer Epidemiol Biomarkers Prev 16:2379-86. 2007
    ..The NAT2*6A/any slow acetylation genotype may be a predisposing factor for pancreatic cancer among diabetics with smoking exposure. Our observations must be confirmed in larger independent studies...
  93. ncbi Acetylator phenotype and genotype in HIV-infected patients with and without sulfonamide hypersensitivity
    Rodger D MacArthur
    Department of Pharmaceutical Sciences, Wayne State University, Detroit, Michigan 48202, USA
    J Clin Pharmacol 42:613-9. 2002
    ....
  94. ncbi GSTM1 null genotype, red meat consumption and breast cancer risk (The Netherlands)
    Olga L van der Hel
    Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, P O Box 85500, 3508 GA Utrecht, The Netherlands
    Cancer Causes Control 15:295-303. 2004
    ..We studied whether polymorphisms in N-acetyltransferase 1 and 2 and Glutathione S-transferase M1 and T1 genes modify the association between meat consumption and breast cancer...

Research Grants20

  1. UofL Environmental Health Sciences Training Program
    David Hein; Fiscal Year: 2007
    ..The University of Louisville has increased its commitment to health science research and infrastructure, graduate education, and minority recruitment, making this training program particularly timely. ..
  2. PHARMACOGENETICS OF DRUG AND CARCINOGEN METABOLISM
    David Hein; Fiscal Year: 2007
    ..We also will assess the effect of NAT1 and NAT2 genotypes in breast cancer risk through participation in ongoing molecular epidemiology investigations of breast cancer in Shanghai China and in Nashville, Tennessee. ..
  3. PHARMACOGENETICS OF DRUG AND CARCINOGEN METABOLISM
    David Hein; Fiscal Year: 2001
    ....
  4. PHARMACOGENETICS OF DRUG AND CARCINOGEN METABOLISM
    David Hein; Fiscal Year: 2009
    ..We also will assess the effect of NAT1 and NAT2 genotypes in breast cancer risk through participation in ongoing molecular epidemiology investigations of breast cancer in Shanghai China and in Nashville, Tennessee. ..