Coke oven workers study: the effect of exposure and GSTM1 and NAT2 genotypes on DNA adduct levels in white blood cells and lymphocytes as determined by -postlabelling

Binková, Blanka; Topinka, Jan; Mračková, Gabriela; Gajdošová, Dagmar; Vidová, Paulı́na; Stávková, Zdena; Peterka, V.; Pilčı́k, Tomáš; Rimár, Vladimı́r; Dobiáš, L.; Farmer, Peter B.; Šrám, Radìm J.

doi:10.1016/s1383-5718(98)00061-8

Cited by 80 publications

(43 citation statements)

References 35 publications

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“…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. In studies reported by Hemminki et al (1997) and Ovrebo et al (1998 ), no significant correlation of GSTM1 or CYP1A1 genotypes to urinary 1 -hydroxypyrene (1 -OHP) was observed in high PAH exposure occupations.…”

Section: Introductionmentioning

confidence: 91%

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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Section: Introductionmentioning

confidence: 91%

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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“…Several studies have noted a lack of significant difference in lymphocyte PAH-DNA adduct levels between GSTM1-deficient and -proficient individuals (Ryberg et al, 1994;Hou et al, 1995;Binkova et al, 1998). However, findings reported by Georgiadis et al (2004) indicate that nonsmoking students exposed to urban air pollution and ETS with GSTM1 deletion had higher levels of DNA adducts in their lymphocytes compared with GSTM1 ''wild-type'' participants.…”

Section: Introductionmentioning

confidence: 98%

Biomarkers of exposure to combustion by-products in a human population in Shanxi, China

Naufal

Zhu

et al. 2009

J Expo Sci Environ Epidemiol

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Emissions of complex mixtures of polycyclic aromatic hydrocarbons (PAHs) and other compounds into the environment represent a potential threat to the health of humans. Information regarding the dose and duration of exposure is essential to determine the degree of risk and to identify sensitive receptors within a population. Although measurements of chemical concentrations in air may be used to estimate exposures, internal biomarkers provide more accurate information regarding the dose of exposure and retention of toxic chemicals. This study was conducted in a population in rural China exposed to PAHs from a variety of sources. The study population was located in an area known to have an elevated incidence of birth defects. Parents of children born with a neural tube defect (NTD) were recruited as case participants and parents of children born with no visible birth defect were recruited as controls. The study was designed to test the hypothesis that parents of children born with a NTD would exhibit a biomarker of exposure at higher levels than the parents of a child with no visible birth defect. A total of 35 mothers and 32 fathers were recruited as case participants, and 18 mothers and 19 fathers were recruited as control participants. Venous blood was collected from the study participants by hospital staff as soon as possible following the birth of the child. PAHs were isolated from the whole blood by solvent extraction and DNA was isolated from a separate aliquot of blood for 32 Ppostlabeling to measure bulky adducts. Single Nucleotide Polymorphisms (SNPs) in phase II enzymes were also monitored in an attempt to identify sensitive receptors. Both total and carcinogenic PAH (cPAH) concentrations were elevated in the parents of case children. Both values were elevated significantly in mothers, whereas only cPAH concentrations were elevated significantly in fathers. Levels of DNA adducts were highly variable and displayed a reverse pattern to that of PAH levels in blood. None of the polymorphisms evaluated were correlated with PAH levels or DNA adducts. For mothers, whose total PAH concentration was above the median concentration, the age-adjusted odds ratio (OR) for having a child with a NTD was 8.7. Although this suggests that PAHs may be a contributing factor to the risk of NTDs, the lack of a correlation with DNA adducts would suggest a possible non-genotoxic mechanism. Alternatively, the PAHs may be a surrogate for a different exposure that is more directly related to the birth defects. The results have shown that blood levels of PAHs may be used to identify populations exposed to elevated concentrations of combustion by-products.

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“…An epidemiological 30-year follow-up study has confirmed that occupational exposure to coke oven emissions is associated with significant excess mortality from cancer of the respiratory system and of the prostate (IARC, 1987;Binkova et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Cytochrome P450 (CYP) and glutathione S-transferases (GST) polymorphisms (CYP1A1, CYP1B1, GSTM1, GSTP1 and GSTT1) and urinary levels of 1-hydroxypyrene in Turkish coke oven workers

et al. 2007

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Genetic polymorphisms of xenobiotic metabolizing enzymes have been associated with cancer risk. We evaluated the influences of genetic polymorphisms of polycyclic aromatic hydrocarbon (PAH) metabolizing enzymes on urinary 1-hydroxypyrene (1-OHP) excretion in Turkish coke oven workers. Urinary 1-OHP was analyzed by HPLC after enzymatic hydrolysis. Lymphocyte DNA was used for PCR-based genotyping of cytochrome P450 (CYP) polymorphisms (CYP1A1 and CYP1B1) and glutathione S-transferases (GST) polymorphisms (GSTM1, GSTT1 and GSTP1). The mean urinary 1-OHP levels of coke oven workers were significantly higher than that of controls. No significant difference was detected in the mean urinary 1-OHP levels of smokers and non-smokers either for coke oven workers or controls. Genetic polymorphisms of the CYPs and GSTs studied had no significant influence on 1-OHP excretion in coke oven workers, but in the control group the urinary 1-OHP levels of individuals carrying the GSTT1-genotype were significantly higher than those of individuals carrying GSTT1+ genotype. The duration of occupational exposure and metabolic genotype for GSTT1 were the significant predictors of urinary 1-OHP levels. The control individuals carrying combined GSTM1-/GSTT1-genotypes also had significantly higher levels of urinary 1-OHP than those of individuals carrying GSTM1+/GSTTI+, GSTM1-/GSTT1+, and GSTM1+/GSTT1-genotypes. These results indicate that urinary 1-OHP is a sensitive indicator of recent human exposure to PAHs and that genetic polymorphism of GSTT1 may also to some extent reflect the interindividual variation in susceptibility to PAHs only at low PAH exposure.

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Coke oven workers study: the effect of exposure and GSTM1 and NAT2 genotypes on DNA adduct levels in white blood cells and lymphocytes as determined by -postlabelling

Cited by 80 publications

References 35 publications

The effect of relevant genotypes on PAH exposure-related biomarkers

The effect of relevant genotypes on PAH exposure-related biomarkers

Biomarkers of exposure to combustion by-products in a human population in Shanxi, China

Cytochrome P450 (CYP) and glutathione S-transferases (GST) polymorphisms (CYP1A1, CYP1B1, GSTM1, GSTP1 and GSTT1) and urinary levels of 1-hydroxypyrene in Turkish coke oven workers

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