Source:http://linkedlifedata.com/resource/pubmed/id/15298956
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rdf:type | |
lifeskim:mentions |
umls-concept:C0000641,
umls-concept:C0005052,
umls-concept:C0023516,
umls-concept:C0026027,
umls-concept:C0059735,
umls-concept:C0080103,
umls-concept:C0242958,
umls-concept:C0337664,
umls-concept:C0441889,
umls-concept:C0919425,
umls-concept:C0919451,
umls-concept:C0919534,
umls-concept:C1333715,
umls-concept:C1882417,
umls-concept:C2247484
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pubmed:issue |
8
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pubmed:dateCreated |
2004-8-9
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/7,8-Dihydro-7,8-dihydroxybenzo(a)pyr...,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP1A1,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Adducts,
http://linkedlifedata.com/resource/pubmed/chemical/Genetic Markers,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/benzo(a)pyrene-7,8-dihydrodiol-9,10-...,
http://linkedlifedata.com/resource/pubmed/chemical/glutathione S-transferase M1
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1055-9965
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1342-8
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pubmed:dateRevised |
2006-11-15
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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
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pubmed:year |
2004
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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.
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pubmed:affiliation |
Department of Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy. maura.lodovici@unifi.it
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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