2.50
Hdl Handle:
http://hdl.handle.net/10146/76634
Title:
Genetic susceptibility to benzene toxicity in humans.
Authors:
Garte, Seymour; Taioli, Emanuela; Popov, Todor; Bolognesi, Claudia; Farmer, Peter; Merlo, Franco
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.
Citation:
J. Toxicol. Environ. Health Part A 2008, 71 (22):1482-1489
Journal:
Journal of toxicology and environmental health. Part A
Issue Date:
2008
URI:
http://hdl.handle.net/10146/76634
DOI:
10.1080/15287390802349974
PubMed ID:
18836923
Additional Links:
http://www.informaworld.com/smpp/content~db=all?content=10.1080/15287390802349974
Type:
Article
Language:
en
ISSN:
1528-7394
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorGarte, Seymour-
dc.contributor.authorTaioli, Emanuela-
dc.contributor.authorPopov, Todor-
dc.contributor.authorBolognesi, Claudia-
dc.contributor.authorFarmer, Peter-
dc.contributor.authorMerlo, Franco-
dc.date.accessioned2009-08-07T07:54:39Z-
dc.date.available2009-08-07T07:54:39Z-
dc.date.issued2008-
dc.identifier.citationJ. Toxicol. Environ. Health Part A 2008, 71 (22):1482-1489en
dc.identifier.issn1528-7394-
dc.identifier.pmid18836923-
dc.identifier.doi10.1080/15287390802349974-
dc.identifier.urihttp://hdl.handle.net/10146/76634-
dc.description.abstractHuman 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.en
dc.language.isoenen
dc.relation.urlhttp://www.informaworld.com/smpp/content~db=all?content=10.1080/15287390802349974en
dc.subjectBenzeneen
dc.subjectChemical Industryen
dc.subjectDNA Damageen
dc.subjectGene Expression Profilingen
dc.subjectGenetic Predisposition to Diseaseen
dc.subjectGenotypeen
dc.subjectOccupational Exposureen
dc.subjectPetroleumen
dc.subjectPolymorphismen
dc.subject.meshAdult-
dc.subject.meshBenzene-
dc.subject.meshBulgaria-
dc.subject.meshChemical Industry-
dc.subject.meshDNA Damage-
dc.subject.meshFemale-
dc.subject.meshGene Expression Profiling-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshGenetic Variation-
dc.subject.meshGenotype-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshOccupational Exposure-
dc.subject.meshPetroleum-
dc.subject.meshPolymorphism, Genetic-
dc.titleGenetic susceptibility to benzene toxicity in humans.en
dc.typeArticleen
dc.identifier.journalJournal of toxicology and environmental health. Part Aen

Related articles on PubMed

All Items in ECNIS-NIOM are protected by copyright, with all rights reserved, unless otherwise indicated.