Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2004-8-9
pubmed:abstractText
Benzo(a)pyrene [B(a)P] diolepoxide (BPDE)-DNA adducts were measured in the leukocytes of 41 healthy smokers using high-performance liquid chromatography coupled with a fluorimetric detector. The correlation between exposure to B(a)P through smoking and BPDE-DNA adduct levels was poor (r = 0.31), although subjects in the high exposure group [B(a)P > 50 ng/d] had a slightly higher level of adducts compared with the less exposed group (mean +/- SE, 1.70 +/- 0.3 versus 1.09 +/- 0.1; P = 0.057). We studied the effect on BPDE-DNA adducts of individual variations in genes controlling B(a)P metabolism, classifying subjects in "low-risk" and "high-risk" genotypes for smoking-related B(a)P DNA damage. The high-risk group included subjects characterized by a combination of increased B(a)P activation [cytochrome P450 1A1 (CYP1A1) MspI and/or exon 7 Ile462Val allele variants and microsomal epoxide hydrolase (mEH) fast activity] and decreased deactivation ability [presence of glutathione S-transferase M1 (GSTM1) null allele and wild-type glutathione S-transferase P1 (GSTP1)]. The low-risk group included smokers with lower B(a)P activation (wild-type CYP1A1, low or intermediate mEH activity) and higher deactivation capacity (active GSTM1, GSTP1 Ile105Val allele). Subjects in the low-risk group had lower levels of BPDE-DNA adducts compared with subjects in the high-risk genotype group; this difference was significant using two markers (CYP1A1 and GSTM1, median +/- SD, 0.77 +/- 1.16 versus 1.89 +/- 0.39; P = 0.03) or three markers (CYP1A1, GSTM1, and GSTP1, median +/- SD, 0.66 +/- 0.93 versus 1.43 +/- 1.17; P = 0.013). The discrimination between groups was reduced when including mEH as an additional marker (P = 0.085). In conclusion, CYP1A1, GSTM1, and GSTP1 genotyping seems to be a risk predictor of BPDE-DNA adduct formation in leukocytes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1055-9965
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1342-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15298956-7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide, pubmed-meshheading:15298956-Adolescent, pubmed-meshheading:15298956-Adult, pubmed-meshheading:15298956-Analysis of Variance, pubmed-meshheading:15298956-Cohort Studies, pubmed-meshheading:15298956-Cytochrome P-450 CYP1A1, pubmed-meshheading:15298956-DNA Adducts, pubmed-meshheading:15298956-Female, pubmed-meshheading:15298956-Genetic Markers, pubmed-meshheading:15298956-Glutathione Transferase, pubmed-meshheading:15298956-Humans, pubmed-meshheading:15298956-Leukocytes, pubmed-meshheading:15298956-Male, pubmed-meshheading:15298956-Middle Aged, pubmed-meshheading:15298956-Polymorphism, Genetic, pubmed-meshheading:15298956-Risk Assessment, pubmed-meshheading:15298956-Sensitivity and Specificity, pubmed-meshheading:15298956-Smoking, pubmed-meshheading:15298956-Statistics, Nonparametric
pubmed:year
2004
pubmed:articleTitle
Benzo(a)pyrene diolepoxide (BPDE)-DNA adduct levels in leukocytes of smokers in relation to polymorphism of CYP1A1, GSTM1, GSTP1, GSTT1, and mEH.
pubmed:affiliation
Department of Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy. maura.lodovici@unifi.it
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't