Aromatic DNA adduct levels in coke oven workers: correlation with polymorphisms in genes GSTP1, GSTM1, GSTT1 and CYP1A1

Teixeira, João Paulo; Gaspar, Jorge; Martinho, Gabriela; Silva, Susana; Rodrigues, Sónia; Mayan, Olga; Martin, Elizabeth A.; Farmer, Peter B.; Rueff, José

doi:10.1016/s1383-5718(02)00063-3

Cited by 48 publications

(27 citation statements)

References 24 publications

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“…However, the results thus far are inconsistent for the effects of glutathione S-transferase polymorphisms on exposure biomarkers in coke-oven workers. For instance, the GSTM1 null genotype was found to be associated with increased levels of benzo(a)pyrene diol epoxide -DNA adducts among the coke-oven workers (21,22), but this association was not confirmed by other studies (23)(24)(25).…”

Section: Introductionmentioning

confidence: 76%

Association of Polymorphisms in AhR, CYP1A1, GSTM1, and GSTT1 Genes with Levels of DNA Damage in Peripheral Blood Lymphocytes among Coke-Oven Workers

Chen

Bai

Yuan

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Accumulating evidence has shown that both DNA damage caused by the metabolites of polycyclic aromatic hydrocarbons (PAH) and genetic polymorphisms in PAH-metabolic genes contribute to individual susceptibility to PAH-induced carcinogenesis. However, the functional relevance of genetic polymorphisms in PAH-metabolic genes in exposed individuals is still unclear. In this study of 240 coke-oven workers (the exposed group) and 123 non -coke-oven workers (the control group), we genotyped for polymorphisms in the AhR, CYP1A1, GSTM1, and GSTT1 genes by PCR methods, and determined the levels of DNA damage in peripheral blood lymphocytes using the alkaline comet assay. We found that the ln-transformed Olive tail moment (Olive TM) values in the exposed group were significantly higher than those in the control group (P < 0.001). Furthermore, in the exposed group, the Olive TM values in subjects with the AhR Lys 554 variant genotype were higher than those with the AhR Arg 554 /Arg 554 genotype (P = 0.021). Similarly, the Olive TM values in the non -coke-oven workers with the CYP1A1 MspI CC + CT genotype were lower than the values of those with the CYP1A1 MspI TT genotype (P = 0.005). However, these differences were not evident for GSTM1 and GSTT1. These results suggested that the polymorphism of AhR might modulate the effects of PAHs in the exposed group; however, the underlying molecular mechanisms by which this polymorphism may have affected the levels of PAH-induced DNA damage warrant further investigation. (Cancer Epidemiol Biomarkers Prev 2006;15(9):1703 -7)

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Section: Introductionmentioning

confidence: 76%

Association of Polymorphisms in AhR, CYP1A1, GSTM1, and GSTT1 Genes with Levels of DNA Damage in Peripheral Blood Lymphocytes among Coke-Oven Workers

Chen

Bai

Yuan

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…DNA adducts have been found to be dependent on polymorphisms in metabolic genes (i.e., MspI polymorphism of CYP1A1 and GSTM1 null genotype; refs. [26][27][28][29][30]. DNA damage may be repaired, but the individual's ability to remove DNA adducts may vary from individual to individual (31,32).…”

Section: Dna Adducts and Lung Cancer Riskmentioning

confidence: 99%

DNA Adducts and Lung Cancer Risk: A Prospective Study

Peluso¹,

Munnia²,

Hoek

et al. 2005

Cancer Research

109

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Objectives were to investigate prospectively the ability of DNA adducts to predict cancer and to study the determinants of adducts, especially air pollutants. DNA adducts were measured in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) investigation. Cases included newly diagnosed lung cancer (n = 115), upper respiratory cancers (pharynx and larynx; n = 82), bladder cancer (n = 124), leukemia (n = 166), and chronic obstructive pulmonary disease or emphysema deaths (n = 77) accrued after a median follow-up of 7 years among the EPIC former smokers and never-smokers. Three controls per case were matched for questionnaire analyses and two controls per case for laboratory analyses. Matching criteria were gender, age, smoking status, country of recruitment, and follow-up time. Individual exposure to air pollution was assessed using concentration data from monitoring stations in routine air quality monitoring networks. Leukocyte DNA adducts were analyzed blindly using 32 P postlabeling technique. Adducts were associated with the subsequent risk of lung cancer, with an odds ratio (OR) of 1.86 [95% confidence interval (95% CI), 0.88-3.93] when comparing detectable versus nondetectable adducts. The association with lung cancer was stronger in never-smokers (OR, 4.04; 95% CI, 1.06-15.42) and among the younger age groups. After exclusion of the cancers occurring in the first 36 months of follow-up, the OR was 4.16 (95% CI, 1.24-13.88). A positive association was found between DNA adducts and ozone (O 3 ) concentration. Our prospective study suggests that leukocyte DNA adducts may predict lung cancer risk of never-smokers. Besides, the association of DNA adduct levels with O 3 indicates a possible role for photochemical smog in determining DNA damage. (Cancer Res 2005; 65(17): 8042-8)

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“…GSTM1 and GSTT1 genotyping for gene deletions was carried out by a multiplex PCR as described by Lin et al [15] with the modifications described by Teixeira et al [16]. All the genotype determinations were carried out twice in independent experiments and all the inconclusive samples were reanalyzed.…”

Section: Genotypingmentioning

confidence: 99%

Role of haemoglobin in the protection of cultured lymphocytes against diepoxybutane (DEB), assessed by in vitro induced chromosome breakage

Porto

Chiecchio

Gaspar

et al. 2003

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Diepoxybutane (DEB) is an alkylating agent that can be used to assess chromosome instability in repair-deficient subjects. Previous authors investigated the role of red blood cells (RBC) in determining individual susceptibility to DEB in normal healthy donors, and demonstrated that a polymorphic enzyme in RBC, Glutathione S-transferase T1 (GSTT1), is involved in DEB detoxification. In the present work we studied the influence of individual GSTM1 and GSTT1 genotypes and the presence of RBC on the frequency of DEB-induced chromosome breakage in lymphocyte cultures from normal individuals and, in particular, the influence of isolated components of RBC: RBC membranes, RBC lysate, and haemoglobin. Our results confirm that individual GSTT1 genotypes modulate the level of genetic lesions induced by DEB; however, this effect was not sufficient to explain the highly significant variation in chromosome breakage between whole blood and RBC-depleted cultures. We showed that RBC can protect cultured lymphocytes against chromosome breakage induced by DEB and we demonstrated the particular role of haemoglobin in the protective effect.

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Aromatic DNA adduct levels in coke oven workers: correlation with polymorphisms in genes GSTP1, GSTM1, GSTT1 and CYP1A1

Cited by 48 publications

References 24 publications

Association of Polymorphisms in AhR, CYP1A1, GSTM1, and GSTT1 Genes with Levels of DNA Damage in Peripheral Blood Lymphocytes among Coke-Oven Workers

Association of Polymorphisms in AhR, CYP1A1, GSTM1, and GSTT1 Genes with Levels of DNA Damage in Peripheral Blood Lymphocytes among Coke-Oven Workers

DNA Adducts and Lung Cancer Risk: A Prospective Study

Role of haemoglobin in the protection of cultured lymphocytes against diepoxybutane (DEB), assessed by in vitro induced chromosome breakage

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