PMID- 11170238
OWN - NLM
STAT- MEDLINE
DCOM- 20010308
LR  - 20191025
IS  - 0893-6692 (Print)
IS  - 0893-6692 (Linking)
VI  - 37
IP  - 1
DP  - 2001
TI  - Variant metabolizing gene alleles determine the genotoxicity of benzo[a]pyrene.
PG  - 17-26
AB  - Understanding the mechanisms involved with genetic susceptibility to 
      environmental disease is of major interest to the scientific community. We have 
      conducted an in vitro study to elucidate the involvement of polymorphic 
      metabolizing genes on the genotoxicity of benzo[a]pyrene (BP). Blood samples from 
      38 donors were treated with BP and the induction of sister chromatid exchanges 
      (SCE) and chromosome aberrations (CA) were evaluated. The latter is based on the 
      tandem-probe fluorescence in situ hybridization (FISH) assay. The data indicate 
      that the induction of genotoxicity was clearly determined by the inherited 
      variant genotypes for glutathione-S-transferase (GSTM1) and microsomal epoxide 
      hydrolase (EH). In a comparison of the two biomarkers, the CA biomarker shows a 
      more definite association with the genotypes than does SCE. For example, the 
      presence of the GSTM1 null genotype (GSTM1 0/0) is responsible for the highest 
      level and significant induction of CA, irrespective of the presence of other 
      genotypes in the different donors. This effect is further enhanced significantly 
      by the presence of the excessive activation EH gene allele (EH4*) and decreased 
      by the reduced activation EH gene allele (EH3*). Overall, the modulation of 
      genotoxicity by the susceptibility genotypes provides support of their potential 
      involvement in environmental cancer. Furthermore, the data indicate that the 
      variant enzymes function independently by contributing their metabolic capability 
      toward the expression of biologic activities. Therefore, studies like this one 
      can be used to resolve the complexity of genetic susceptibility to environmental 
      disease in human.
CI  - Copyright 2001 Wiley-Liss, Inc.
FAU - Salama, S A
AU  - Salama SA
AD  - Department of Preventive Medicine and Community Health, The University of Texas 
      Medical Branch, 700 Harborside Drive, Galveston, TX 77555-1110, USA.
FAU - Sierra-Torres, C H
AU  - Sierra-Torres CH
FAU - Oh, H Y
AU  - Oh HY
FAU - Hamada, F A
AU  - Hamada FA
FAU - Au, W W
AU  - Au WW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Environ Mol Mutagen
JT  - Environmental and molecular mutagenesis
JID - 8800109
RN  - 0 (Biomarkers)
RN  - 3417WMA06D (Benzo(a)pyrene)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - EC 2.5.1.18 (glutathione S-transferase M1)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Adult
MH  - *Alleles
MH  - Benzo(a)pyrene/metabolism/*toxicity
MH  - Biomarkers/blood
MH  - Biotransformation/*genetics
MH  - Chromosome Aberrations
MH  - Epoxide Hydrolases/genetics/metabolism
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Glutathione Transferase/genetics/metabolism
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lymphocytes/*drug effects/metabolism/pathology
MH  - Middle Aged
MH  - Mutagenicity Tests
MH  - Polymorphism, Genetic
MH  - Predictive Value of Tests
MH  - Sister Chromatid Exchange/drug effects/genetics
EDAT- 2001/02/15 11:00
MHDA- 2001/03/10 10:01
CRDT- 2001/02/15 11:00
PHST- 2001/02/15 11:00 [pubmed]
PHST- 2001/03/10 10:01 [medline]
PHST- 2001/02/15 11:00 [entrez]
AID - 10.1002/1098-2280(2001)37:1<17::AID-EM1002>3.0.CO;2-F [pii]
AID - 10.1002/1098-2280(2001)37:1<17::aid-em1002>3.0.co;2-f [doi]
PST - ppublish
SO  - Environ Mol Mutagen. 2001;37(1):17-26. doi: 
      10.1002/1098-2280(2001)37:1<17::aid-em1002>3.0.co;2-f.