Abstract

A program of pharmacogenetic investigation in drug metabolism, and toxicity of drugs and other environmental chemicals is proposed. The investigations will be performed in human families, in genetically defined experimental animal models, and subcellular systems of human and animal tissues. This is an interdisciplinary program combining investigators from pharmacology and human and mouse genetics with extensions into biological chemistry, toxicology and molecular biology. Specifically, the program will undertake 1) studies to determine the structural and functional nature of isozymic differences of rapid and slow acetylator N-acetyltransferases; 2) experimental and clinical studies to determine the significance and relationship of human serum esterases to organophosphate toxicity and drug metabolism; and 3) molecular biology (gene cloning) studies to determine whether the hereditary difference in the usual human serum cholinesterase and its isozymic variants are accounted for by DNA polymorphisms.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
2P01GM027028-06A1
Application #
3096075
Study Section
Pharmacology-Toxicology Review Committee (PTR)
Project Start
1980-01-01
Project End
1990-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Voice, R A; Manis, M; Weber, W W (1993) Inhibition of human red blood cell N-acetyltransferase. Drug Metab Dispos 21:181-3
Smolen, T N; Brewer, J A; Weber, W W (1993) Testosterone modulation of N-acetylation in mouse kidney. J Pharmacol Exp Ther 264:854-8
Martell, K J; Weber, W W (1993) N-acetylation polymorphism in liver and pancreas of inbred rats. Drug Metab Dispos 21:965-6
Weber, W W; Vatsis, K P (1993) Individual variability in p-aminobenzoic acid N-acetylation by human N-acetyltransferase (NAT1) of peripheral blood. Pharmacogenetics 3:209-12
Adkins, S; Gan, K N; Mody, M et al. (1993) Molecular basis for the polymorphic forms of human serum paraoxonase/arylesterase: glutamine or arginine at position 191, for the respective A or B allozymes. Am J Hum Genet 52:598-608
Levy, G N; Weber, W W (1992) 2-Aminofluorene-DNA adducts in mouse urinary bladder: effect of age, sex and acetylator phenotype. Carcinogenesis 13:159-64
Bartels, C F; Jensen, F S; Lockridge, O et al. (1992) DNA mutation associated with the human butyrylcholinesterase K-variant and its linkage to the atypical variant mutation and other polymorphic sites. Am J Hum Genet 50:1086-103
Bartels, C F; James, K; La Du, B N (1992) DNA mutations associated with the human butyrylcholinesterase J-variant. Am J Hum Genet 50:1104-14
Jensen, F S; Bartels, C F; La Du, B N (1992) Structural basis of the butyrylcholinesterase H-variant segregating in two Danish families. Pharmacogenetics 2:234-40
Martell, K J; Vatsis, K P; Weber, W W (1991) Molecular genetic basis of rapid and slow acetylation in mice. Mol Pharmacol 40:218-27

Showing the most recent 10 out of 53 publications