Carcinogenesis Advance Access published online on October 7, 2004
Carcinogenesis, doi:10.1093/carcin/bgh303
© 2004 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Occupational Health Section, Department of Environmental Medicine and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova (Italy)
* To whom correspondence should be addressed. E-mail: sofia.pavanello{at}unipd.it.
It is important to identify potential genetic-susceptible factors able to modulate individual responses to exposure to the carcinogenic polycyclic aromatic hydrocarbons (PAHs). In the present study we evaluated the influence of four polymorphisms of nucleotide excision repair (NER) genes (XPC-PAT +/-, XPA 5' non-coding region-A23G, XPD- exon 23 A35931C Lys 751Gln, XPD- exon 10 G23591A Asp312Asn) and that of glutathione S-transferase µ 1 (GSTM1-active or -null) on benzo[a]pyrene diol epoxide (B[a]PDE)-DNA adduct levels from the lympho-monocyte fraction (LMF) of highly PAH (B[a]P)-exposed Polish coke oven workers (n=67, 67% current smokers) with individual urinary post-shift excretion of 1-pyrenol exceeding the proposed BEI (2.28 µmol/mol creatinine). The bulky anti-B[a]PDEDNA adduct levels were detected by HPLC/fluorescence analysis and genotypes by PCR. We found that workers with the low DNA repair capacity of XPC-PAT +/+ and XPA-A23A genotypes had significantly increased anti-B[a]PDE-DNA adduct levels (Mann-Whitney U-test, z=2.24, p=0.02 and z=2.65 p=0.01). Moreover, DNA adducts were also raised in workers without GSTM1 activity (GSTM1 null genotype) (Mann-Whitney U-test, z=2.25, p=0.0246). Workers with unfavourable XPCPAT +/+ and XPA-A23A NER genotypes, alone (about 65% of workers) or combined with GSTM1-null genotype (about 75% of workers) were in the tertile with the highest adduct level i.e., >4.11 adducts /108 nucleotides (Chi2 =5.85, p=0.0156 and Chi2 =5.40, p=0.01). The increase in anti-B[a]PDE-DNA adduct levels (ln values) were significantly related in a multiple linear regression analysis to PAH exposure (i.e., urinary post-shift excretion of 1-pyrenol) (t=2.61, p=0.0115), lack of GSTM1 activity (t=2.41, p=0.0192) and to low DNA repair capacity of XPC-PAT +/+ genotype (t=2.34, p=0.0226). The influence of the XPA-A23A genotype was not evident in this statistical analysis, and no associations with XPD polymorphisms, dietary habits or tobacco smoking were found. The modulation of anti-B[a]PDE-DNA adducts in the LMF by GSTM1-null and some low-activity NER genotypes may be considered as a potential genetic susceptibility factor capable of modulating individual responses to PAH (B[a]P) genotoxic exposure and the consequent risk of cancer in coke oven workers.
Revised September 1, 2004
Accepted September 29, 2004
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Reduced nucleotide excision repair and GSTM1 null genotypes influence ANTI-B[a]PDE-DNA adduct levels in mononuclear white blood cells of highly PAH-exposed coke oven workers
2 Institute of Occupational Health, Sosnowiec (Poland)
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Pavanello, L. Kapka, E. Siwinska, D. Mielzynska, C. Bolognesi, and E. Clonfero Micronuclei Related to Anti-B[a]PDE-DNA Adduct in Peripheral Blood Lymphocytes of Heavily Polycyclic Aromatic Hydrocarbon-Exposed Nonsmoking Coke-Oven Workers and Controls Cancer Epidemiol. Biomarkers Prev., October 1, 2008; 17(10): 2795 - 2799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Qiu, S. Leng, Z. Wang, Y. Dai, Y. Zheng, and Z. Wang Path Analysis of Biomarkers of Exposure and Early Biological Effects among Coke-Oven Workers Exposed to Polycyclic Aromatic Hydrocarbons Cancer Epidemiol. Biomarkers Prev., June 1, 2007; 16(6): 1193 - 1199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. I. Berndt, E. A. Platz, M. D. Fallin, L. W. Thuita, S. C. Hoffman, and K. J. Helzlsouer Genetic Variation in the Nucleotide Excision Repair Pathway and Colorectal Cancer Risk. Cancer Epidemiol. Biomarkers Prev., November 1, 2006; 15(11): 2263 - 2269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Garcia-Closas, N. Malats, F. X. Real, R. Welch, M. Kogevinas, N. Chatterjee, R. Pfeiffer, D. Silverman, M. Dosemeci, A. Tardon, et al. Genetic variation in the nucleotide excision repair pathway and bladder cancer risk. Cancer Epidemiol. Biomarkers Prev., March 1, 2006; 15(3): 536 - 542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-Y. Huang, S. I. Berndt, D. Kang, N. Chatterjee, S. J. Chanock, M. Yeager, R. Welch, R. S. Bresalier, J. L. Weissfeld, and R. B. Hayes Nucleotide Excision Repair Gene Polymorphisms and Risk of Advanced Colorectal Adenoma: XPC Polymorphisms Modify Smoking-Related Risk. Cancer Epidemiol. Biomarkers Prev., February 1, 2006; 15(2): 306 - 311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Bigler, C. M. Ulrich, T. Kawashima, J. Whitton, and J. D. Potter DNA Repair Polymorphisms and Risk of Colorectal Adenomatous or Hyperplastic Polyps Cancer Epidemiol. Biomarkers Prev., November 1, 2005; 14(11): 2501 - 2508. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hoffmann, C. Isner, J. Hogel, and G. Speit Genetic polymorphisms and the effect of cigarette smoking in the comet assay Mutagenesis, September 1, 2005; 20(5): 359 - 364. [Abstract] [Full Text] [PDF]
|
|