Polycyclic Aromatic Hydrocarbon-DNA Adducts in Smokers and Their Relationship to Micronutrient Levels and Glutathione-S-Transferase M1 Genotype

Grinberg-Funes, Ricardo A.; Singh, Vir; Perera, Frederica P.; Bell, Douglas A.; Young, Tie Lan; Dickey, Christopher; Wang, Lian W.; Santella, Regina M.

doi:10.1007/978-1-4612-0237-0_12

Cited by 6 publications

(11 citation statements)

References 38 publications

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“…Yet the study did not show any association between GSTM1 genotypes and the levels of other plasma micronutrients: b-cryptoxanthin, lutein, lycopene, zeaxanthin, retinal, and total carotenoids [27]. Similarly, some authors also reported inverse associations between plasma antioxidant levels and DNA adducts in individuals with specific GST polymorphisms [10,22]. In the present study, some association between antioxidative defense markers and GST genetic polymorphisms also occurs in the lung cancer patients, however, it is less pronounced than in controls.…”

Section: Discussionmentioning

confidence: 68%

Antioxidant defense markers modulated by glutathione S-transferase genetic polymorphism: results of lung cancer case–control study

2007

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Section: Discussionmentioning

confidence: 68%

Antioxidant defense markers modulated by glutathione S-transferase genetic polymorphism: results of lung cancer case–control study

2007

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“…Many studies have revealed no or only a tentative effect of the GSTM1 null genotype on DNA adducts or urinary metabolites of PAHs ( Grinberg -Funes et al, 1994;Hemminki et al, 1997;Mooney et al, 1997;Motykiewicz et al, 1998;Nielsen et al, 1996 ). Instead, Binkova et al, 1998 reported a significant effect of the GSTM1 null genotype on urinary PAH metabolites and mutagenicity, but no effect on DNA adducts in WBCs of an environmentally exposed nonsmoking population.…”

Section: Introductionmentioning

confidence: 99%

“…Fereira et al ( 1994 ) concluded in a cross -sectional study on coke and graphiteelectrode -producing plant workers that, on a group level, urinary mutagenicity might contribute to the detection of workers exposed to genotoxic PAHs. Recently it has been demonstrated that PAH exposure-related urinary mutagenicity might vary depending on an individual's genetic characteristics (Bartsch et al, 1995;Gabbani et al, 1996;Hirvonen et al, 1994 ).Many studies have revealed no or only a tentative effect of the GSTM1 null genotype on DNA adducts or urinary metabolites of PAHs ( Grinberg -Funes et al, 1994;Hemminki et al, 1997;Mooney et al, 1997;Motykiewicz et al, 1998;Nielsen et al, 1996 ). Instead, Binkova et al, 1998 reported a significant effect of the GSTM1 null genotype on urinary PAH metabolites and mutagenicity, but no effect on DNA adducts in WBCs of an environmentally exposed nonsmoking population.…”

mentioning

confidence: 99%

The effect of relevant genotypes on PAH exposure-related biomarkers

Kuljukka-Rabb

Nylund

Vaaranrinta

et al. 2002

J Expo Sci Environ Epidemiol

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Polycyclic aromatic hydrocarbons ( PAHs ) in coke oven emissions cause a cancer risk to humans. In a comprehensive biomonitoring study among Estonian coke oven workers, we looked at the effect of genetic polymorphisms in metabolic enzymes on urinary mutagenicity, 1 -hydroxypyrene ( 1 -OHP ) concentration in urine, and aromatic DNA adducts in white blood cells ( WBCs ). Coke oven workers were sampled twice ( samplings I and II ), and controls only once at the time of sampling I. Urinary mutagenicity was measured using the Ames test. CYP1A1, microsomal epoxide hydrolase ( mEH ), and glutathione S -transferase ( GST ) genotypes were analyzed by polymerase chain reaction ( PCR ). Urinary mutagenicity did not differ between exposed and controls, but those coke oven workers who were smokers had significantly higher ( P= 0.0002 ) mutagenic activity in urine than nonsmokers. Urinary mutagenicity was moderately correlated to levels of 1 -OHP and aromatic DNA adducts, the P values ranging from 0.0005 to 0.002. Carriers of a variant allele in exon 4 of mEH ( Arg 139 ) had elevated urinary mutagenicity ( sampling I ). In addition, urine mutagenicity of persons with predicted high mEH activity was significantly higher. Smoking habit did not explain the differences observed in urinary mutagenicity between mEH phenotype or genotype subgroups. Variation in exon 3 of mEH ( His 113 ) was related to a significantly ( P= 0.01 ) higher 1 -OHP concentration in exposed workers ( sampling II ). Workers from sampling I who had an Arg 139 variation in mEH had lower levels of adducts in lymphocytes ( P= 0.01 ) than others, while airborne benzo[ a ]pyrene ( B[ a ]P ) and His 113 variation affected interactively on adduct levels. Our study shows that a comprehensive assessment of exposure is essential for elucidation of PAH exposure at a workplace. Even at high exposures metabolic polymorphisms seem to have some effect on biomarker levels, and should be assessed in biomonitoring studies. Journal of Exposure Analysis and Environmental Epidemiology ( 2002 ) 12, 81 -91 DOI: 10.1038 / sj / jea / 7500204Keywords: aromatic DNA adducts, coke oven workers, genetic polymorphism, 1 -hydroxypyrene, urine mutagenicity. IntroductionEpidemiological data show that exposure to polycyclic aromatic hydrocarbons (PAHs ) is possibly carcinogenic to humans and believed to be mainly responsible for an elevated lung cancer incidence among coke oven workers (International Agency for Research on Cancer (IARC ), 1983;( International Agency for Research on Cancer (IARC ), 1984 ). In addition, other carcinogens, such as aromatic amines and heterocyclic compounds, are known to be present in coke oven emissions (IARC, 1984). Recent studies reveal both high and low mean exposure levels in operating coke oven plants.Most carcinogenic chemicals, such as PAHs, need to be activated to electrophilic reactants by metabolism in vivo (Miller and Miller, 1981 ). It is known at present that many of the genes coding enzymes involved in activation and detoxification of PAHs are poly...

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“…Allhough the va lidity of MNC DNA adducts as markers of Ihe effects of dietary anlioxidanls on lung DNA damage requires addilional study, these results are consistenl with Ihe epidemiological data that indicate that intake of carolenoids, vilamin A, and foods conlaining Ihese nulrienls are slrongly associated wilh decreased lung cancer risk (10,11). Other researchers, who used an ELISA method to measure DNA adducts, found an inverse correlation of adduci levels in white blood cells with serum anlioxidanl levels bui noi wilh self-reported dietary inlake (45). Differences in Ihe analylic sensilivity and specificily of adduci deleclion by immunological melhods and Ihe 32P-posllabeling assay lhal influence assessmenl of dielary antioxidants warranl addilional sludy.…”

Section: Discussionmentioning

confidence: 83%

Correlation of DNA adducts in blood mononuclear cells with tobacco carcinogen-induced damage in human lung

Wiencke

Kelsey²,

Várkonyi³

et al. 1996

Lung Cancer

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The formation of carcinogen-DNA adducts within the respiratory epi thelium is thought to be a critical factor in the induction of lung cancer from tobacco smoke. A reliable surrogate measure of carcinogen damage to the lung would be of great value in molecular epidemiological studies of cancer risk. The validity of measurements of DNA adducts formed from hydrophobic aromatic hydrocarbons in peripheral blood mononuclear cells IMNCs) was investigated by comparing the levels of aromatic DNA adducts detected in lung tissue from 31 lung cancer patients with those detected in MNCs from the same individuals using the 32P-postlabeling assay. The associations of smoking history and intake of dietary antioxidants with adduct levels also were assessed. Tissue-specific, as well as common DNA adducts were detected in lung and blood; total MNC adduct levels were highly correlated with total lung adducts. After smok ing cessation, adduct levels appeared to decay in both tissues at similar rates. Multivariate analyses (Poisson regression modeling) indicated that dietary antioxidant intake (carotenoids, vitamin A, and retinol) modified the levels of aromatic DNA adducts in both the lungs and blood. Of all models tested, the optimal one for predicting lung adduct levels included the measure of blood MNC adduct levels only. Therefore, blood MNCs are a valid surrogate tissue for estimating the burden of DNA adducts in respiratory tissue in molecular epidemiological studies.

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Polycyclic Aromatic Hydrocarbon-DNA Adducts in Smokers and Their Relationship to Micronutrient Levels and Glutathione-S-Transferase M1 Genotype

Cited by 6 publications

References 38 publications

Antioxidant defense markers modulated by glutathione S-transferase genetic polymorphism: results of lung cancer case–control study

Antioxidant defense markers modulated by glutathione S-transferase genetic polymorphism: results of lung cancer case–control study

The effect of relevant genotypes on PAH exposure-related biomarkers

Correlation of DNA adducts in blood mononuclear cells with tobacco carcinogen-induced damage in human lung

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