Impact of metabolic genotypes on levels of biomarkers of genotoxic exposure

B. Schoket, Gizella Papp, Katalin Lévay, Gabriela Mracková, Fred F. Kadlubar, István Vincze

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Phase I and Phase II xenobiotic-metabolising enzyme families are involved in the metabolic activation and detoxification of various classes of environmental carcinogens. Particular genetic polymorphisms of these enzymes have been shown to influence individual cancer risk. A brief overview is presented about recent research of the relationship between metabolic genotypes and internal dose, biologically effective dose and cytogenetic effects of complex and specific genotoxic exposures of human study populations, and we report our new results from two molecular epidemiological studies. We investigated the effects of multiple interactions among CYP1A1 Ile462Val, CYP1A1 MspI, CYP1B1 Leu432Val, CYP2C9 Arg144Cys, CYP2C9 Ile359Leu, NQO1 Pro189Ser, GSTM1 gene deletion and GSTP1 Ile105Val genotypes on the levels of carcinogen-DNA adducts determined by 32P-postlabelling and PAH-DNA immunoassay in peripheral blood lymphocytes from workers occupationally exposed to polycyclic aromatic hydrocarbons in aluminium plants, and in bronchial tissue from smoking lung patients. A statistically significant positive linear correlation was observed between white blood cell aromatic DNA adduct and urinary 1-hydroxypyrene (1-OHPY) levels from potroom workers with GSTM1 null genotype (P = 0.011). Our results suggest interactions between GSTM1 and GSTP1 alleles in modulation of urinary 1-OHPY levels and white blood cell DNA adduct levels in the PAH-exposed workers. Interactions between GSTM1 and GSTP1 alleles, in association with particular genotype combinations of CYPs, were also recognised in bronchial aromatic DNA adduct levels of smoking lung patients. The impact of single metabolic genotypes and their combinations on biomarkers of exposure was usually weak, if any, in both our studies and reports of the literature. The effect of special metabolic gene interactions may be better recognised if the compared groups of individuals are stratified for multiple potential modulators of the observable biomarker end-point, and/or if chemical structure-specific biomarker methods are applied.

Original languageEnglish
Pages (from-to)57-69
Number of pages13
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume482
Issue number1-2
Publication statusPublished - Oct 1 2001

Fingerprint

DNA Adducts
Biomarkers
Genotype
Cytochrome P-450 CYP1A1
Leukocytes
Smoking
Alleles
Environmental Carcinogens
Lung
Polycyclic Aromatic Hydrocarbons
Gene Deletion
Xenobiotics
Genetic Polymorphisms
Enzymes
Aluminum
Immunoassay
Cytogenetics
Carcinogens
Epidemiologic Studies
Lymphocytes

Keywords

  • 1-Hydrozypyrene
  • Biomarker
  • DNA adduct
  • Genetic polymorphism
  • Genotoxic exposure
  • Metabolic genotype
  • Molecular epidemiology
  • Polycyclic aromatic hydrocarbons

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

Cite this

Impact of metabolic genotypes on levels of biomarkers of genotoxic exposure. / Schoket, B.; Papp, Gizella; Lévay, Katalin; Mracková, Gabriela; Kadlubar, Fred F.; Vincze, István.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 482, No. 1-2, 01.10.2001, p. 57-69.

Research output: Contribution to journalArticle

Schoket, B. ; Papp, Gizella ; Lévay, Katalin ; Mracková, Gabriela ; Kadlubar, Fred F. ; Vincze, István. / Impact of metabolic genotypes on levels of biomarkers of genotoxic exposure. In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 2001 ; Vol. 482, No. 1-2. pp. 57-69.
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