Genetic susceptibility to benzene toxicity in humans

Seymour Garte, Emanuela Taioli, Todor Popov, Claudia Bolognesi, Peter Farmer, Franco Merlo

Research output: Contribution to journalArticle

Abstract

Human metabolism of benzene involves pathways coded for by polymorphic genes. To determine whether the genotype at these loci might influence susceptibility to the adverse effects of benzene exposure, 208 Bulgarian petrochemical workers and controls, whose exposure to benzene was determined by active personal sampling, were studied. The frequency of DNA single-strand breaks (DNA-SSB) was determined by alkaline elution, and genotype analysis was performed for five metabolic loci. Individuals carrying the NAD(P)H:quinone oxidoreductase 1 (NQO1) variant had significantly twofold increased DNA-SSB levels compared to wild-type individuals. The same result was observed for subjects with microsomal epoxide hydrolase (EPHX) genotypes that predict the fast catalytic phenotype. Deletion of the glutathione S-transferase T1 (GSTT1) gene also showed a consistent quantitative 35-40% rise in DNA-SSB levels. Neither glutathione S-transferase M1 (GSTM1) nor myeloperoxidase (MPO) genetic variants exerted any effect on DNA-SSB levels. Combinations of two genetic polymorphisms showed the same effects on DNA-SSB as expected from the data on single genotypes. The three locus genotype predicted to produce the highest level of toxicity, based on metabolic pathways, produced a significant 5.5-fold higher level of DNA-SSB than did the genotype predicted to yield the least genotoxicity.

Original languageEnglish
Pages (from-to)1482-1489
Number of pages8
JournalJournal of Toxicology and Environmental Health - Part A: Current Issues
Volume71
Issue number22
DOIs
Publication statusPublished - Jan 2008

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Single-Stranded DNA Breaks
Genetic Predisposition to Disease
Benzene
Toxicity
Genotype
DNA
Genes
Exposure controls
Epoxide Hydrolases
Genetic Polymorphisms
Metabolic Networks and Pathways
Polymorphism
Metabolism
Petrochemicals
NAD
Peroxidase
Oxidoreductases
Sampling
Phenotype

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Toxicology

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Genetic susceptibility to benzene toxicity in humans. / Garte, Seymour; Taioli, Emanuela; Popov, Todor; Bolognesi, Claudia; Farmer, Peter; Merlo, Franco.

In: Journal of Toxicology and Environmental Health - Part A: Current Issues, Vol. 71, No. 22, 01.2008, p. 1482-1489.

Research output: Contribution to journalArticle

Garte, S, Taioli, E, Popov, T, Bolognesi, C, Farmer, P & Merlo, F 2008, 'Genetic susceptibility to benzene toxicity in humans', Journal of Toxicology and Environmental Health - Part A: Current Issues, vol. 71, no. 22, pp. 1482-1489. https://doi.org/10.1080/15287390802349974
Garte, Seymour ; Taioli, Emanuela ; Popov, Todor ; Bolognesi, Claudia ; Farmer, Peter ; Merlo, Franco. / Genetic susceptibility to benzene toxicity in humans. In: Journal of Toxicology and Environmental Health - Part A: Current Issues. 2008 ; Vol. 71, No. 22. pp. 1482-1489.
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