Aromatic DNA adducts in coke-oven workers, in relation to exposure, lifestyle and genetic polymorphism of metabolic enzymes

Zhang, J.; Ichiba, Masayoshi; Feng, Yi; Pan, Guowei; Hanaoka, Tomoyuki; Yamano, Yuko; Hara, Kunio; Takahashi, Ken; Tomokuni, Katsumaro

doi:10.1007/s004200050018

Cited by 27 publications

(11 citation statements)

References 43 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: 58%

“…Although it is well known that GSTM1 can detoxify reactive metabolites of benzo(a)pyrene and other PAHs (38), and that the homozygous deletion of GSTM1 leads to the loss of GSTM1 functions (17), several studies have shown that the coke-oven workers without the GSTM1 allele did not have a higher risk of having high benzo(a)pyrene diol epoxide -DNA adduct levels compared with individuals with the GSTM1 non -null genotype (23)(24)(25). In the present study, it was found that this GSTM1 polymorphism was not associated with the levels of DNA damage in the coke-oven workers.…”

Section: Discussionmentioning

confidence: 99%

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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: 58%

Section: Discussionmentioning

confidence: 99%

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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“…Notably, most previous studies measured urinary and/or blood biomarkers at the end of a work shift as a single measurement (5,7,26,32,33). These readings may be affected by the known circadian variation in certain biomarker level (e.g., 8-oxodG; ref.…”

Section: Discussionmentioning

confidence: 99%

Repeated Measurements of Urinary Methylated/Oxidative DNA Lesions, Acute Toxicity, and Mutagenicity in Coke Oven Workers

Chao¹,

Wang

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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We conducted a repeated-measures cohort study of coke oven workers to evaluate the relationships between the traditional exposure biomarker, urinary 1-hydroxypyrene (1-OHP), and a series of biomarkers, including urinary 8-oxo-7,8-dihydro-2 ¶-deoxyguanosine (8-oxodG), N7-methylguanine (N7-MeG), acute toxicity, and mutagenicity. A total of eight spot urine samples were collected from each high-exposed (at topside oven area) and low-exposed workers (at side oven area) during the whole working cycle, which consisted of 6 consecutive days of working followed by 2 days off. Our results showed that the high-exposed workers had significantly higher urinary levels of 1-OHP, 8-oxodG, and N7-MeG compared with the low-exposed workers. Acute toxicity and mutagenicity of urine were also found to be markedly increased in the high-exposed workers, as determined by Microtox assay and Ames test, respectively. Multivariate regressions analysis revealed that the urinary 8-oxodG, N7-MeG, or acute toxicity was significantly correlated with 1-OHP concentrations. Overall, the present study showed that exposure to coke oven emissions increased oxidatively damaged DNA products and mutagenicity of urine, and for the very first time, such exposure was also found to increase DNA methylation and urinary acute toxicity. The potential source of methylating agents in coke oven emissions warrants further investigation. Additionally, with repeated measurements, the pattern of time course for urinary 1-OHP was found to be different from those of 8-oxodG and N7-MeG, as well as acute toxicity and mutagenicity. This finding implies that the single measurement that was often conducted in occupational healthy investigations should be used with certain precautions, because single measurement may fail to provide the proper information of interest. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3381 -9)

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“…Some studies suggest that these variants are associated with DNA adduct levels in lymphocytes of subjects occupationally exposed to PAHs. [32][33][34] One study suggests that the m1 variant affects oestrogen metabolism.…”

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confidence: 99%

“…The functional effects of the other variants are summarized in Table I. [26][27][28][29][30][31][32][33][34][35][36][37] As the presence of the CYP1A1*2A (m1) and CYP1A1*2C (m2) variants appear to be associated with higher levels of biomarkers for PAH exposure, it might be expected that the m1 and m2 variants would be associated with an increased risk for colorectal cancer. However, the results of previous studies of colorectal neoplasia and the CYP1A1 m1 16,41-52 and m2 16,42,44,46,[48][49][50][51][52][53][54][55] genotypes have been inconsistent.…”

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confidence: 99%

Colorectal cancer and genetic polymorphisms of CYP1A1, GSTM1 and GSTT1: A case‐control study in the Grampian region of Scotland

Little

Sharp

Masson

et al. 2006

Intl Journal of Cancer

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Cytochrome P-450 CYP1A1 is involved in the metabolism of polycyclic aromatic hydrocarbons (PAHs) that are derived from meat intake and tobacco smoking. Expression of the CYP1A1 gene is induced by compounds present in cruciferous vegetables. The glutathione S-transferases play a central role in the detoxification of carcinogens, including PAHs. We investigated the association between colorectal cancer and three variants (CYP1A1*2A, CYP1A1*2C, CYP1A1*4) of the CYP1A1 gene, and homozygosity for the null deletion of the GSTM1 and GSTT1 genes, and the joint effects of these genotypes and smoking, meat intake and intake of green leafy vegetables in a population-based study of 264 cases and 408 controls in Northeast Scotland. There was an inverse association with the CYP1A1*4 (m4) variant (OR 0.3, 95% CI 0.13-0.70). The OR for the CYP1A1*2C (m2) variant was 1.3 (95% CI 0.59-2.91), which is similar to a combined estimate for previous studies (OR 1.2, 95% CI 0.95-1.41). We observed no association with the CYP1A1*2A (m1) variant, or the GSTM1 and GSTT1 polymorphisms. Significant interactions between all 3 CYP1A1 variants and meat intake, and between the m1 and m2 variants and intake of green leafy vegetables, were observed. There was no evidence of interaction between CYP1A1 and smoking, and no evidence of interaction between the GSTM1 or GSTT1 polymorphisms and smoking, meat intake, green leafy vegetable intake, CYP1A1 variants or each other. ' 2006 Wiley-Liss, Inc.Key words: colorectal neoplasms; cytochrome P-450 CYP1A1; GSTM1 protein; glutathione S-transferase T1; polymorphism Evidence on the association between colorectal cancer and consumption of cooked meats, 1 tobacco smoking 2,3 and vegetable intake, 4-6 all of which are modifiable exposures with a potentially major public health impact, is inconsistent. Randomized trials 7,8 have confirmed evidence from most observational studies, [9][10][11][12] indicating an inverse relation between postmenopausal oestrogen replacement therapy and colorectal cancer, but considerable heterogeneity in the magnitude of this association was apparent. It is possible that these inconsistencies are in part due to differences between populations in the frequency of variants of genes, whose products modulate the effects of these exposures.A possible unifying factor underlying exposure to cooked meats, tobacco smoke and postmenopausal oestrogen replacement therapy is the presence of polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines. Cooking of meat and fish results in the formation of PAHs and, particularly at high temperatures, heterocyclic amines, which are carcinogenic in animals. [13][14][15] Tobacco smoking is another source of PAH exposure.16 PAHs affect oestrogen production and metabolism. 17CYP1A1 is expressed in the large bowel. 18,19 Because of the involvement of CYP1A1 in the metabolism of PAHs and oestrogens, and perhaps cruciferous vegetables and heterocyclic amines [20][21][22][23][24][25] (Table I), it might be expected that CYP1A1 variants might influence t...

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Aromatic DNA adducts in coke-oven workers, in relation to exposure, lifestyle and genetic polymorphism of metabolic enzymes

Cited by 27 publications

References 43 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

Repeated Measurements of Urinary Methylated/Oxidative DNA Lesions, Acute Toxicity, and Mutagenicity in Coke Oven Workers

Colorectal cancer and genetic polymorphisms of CYP1A1, GSTM1 and GSTT1: A case‐control study in the Grampian region of Scotland

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