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The effect of relevant genotypes on PAH exposure-related biomarkers

Journal of Exposure Science & Environmental Epidemiology volume 12, pages 81–91 (2002)Cite this article

Abstract

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 (Arg139) 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 (His113) was related to a significantly (P=0.01) higher 1-OHP concentration in exposed workers (sampling II). Workers from sampling I who had an Arg139 variation in mEH had lower levels of adducts in lymphocytes (P=0.01) than others, while airborne benzo[a]pyrene (B[a]P) and His113 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.

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Abbreviations

B[a]P:

benzo[a]pyrene

1-OHP:

1-hydroxypyrene

PAH:

polycyclic aromatic hydrocarbon

CYP:

cytochrome P450

GST:

glutathione S-transferase

mEH :

microsomal epoxide hydrolase

BPDE:

benzo[a]pyrene-dihydrodiol-epoxide

WBC:

white blood cell

PCR/RFLP:

polymerase chain reaction/restriction fragment length polymorphism

DMSO:

dimethyl sulfoxide

Ile:

isoleucine

Val:

valine

Ala:

alanine

Tyr:

tyrosine

His:

histidine

Arg:

arginine

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Acknowledgements

The authors thank the volunteers of the RAS “Kiviter” plant who participated in this study and other employees whose contribution was essential in this study. The personnel of Institute of Experimental and Clinical Medicine, in Tallinn are thanked for practical arrangements on site. Diari Ghafouri is thanked for skillful performance of the genotype analyses. All the employees of Finnish Institute of Occupational Health are thanked for their contribution during this study. The research was supported by the Academy of Finland, and the CEC project ERBCIPA CT92-3016.

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Authors and Affiliations

  1. Institute of Occupational Health, Helsinki, FIN-00250, Finland

    TERHI KULJUKKA-RABB, RAIJA VAARANRINTA, KIRSTI SAVELA & KIMMO PELTONEN

  2. National Product Control Agency for Welfare and Health, Helsinki, FIN-00530, Finland

    LARS NYLUND

  3. Karolinska Institute and National Institute for Working Life, Stockholm, Sweden

    AGNETA RANNUG

  4. Department of Epidemiology and Biostatistics, FIOH, Helsinki, FIN-00250, Finland

    PERTTI MUTANEN

  5. Institute of Experimental and Clinical Medicine, Tallinn, Estonia

    TOOMAS VEIDEBAUM

  6. Ministry of Education, Helsinki, FIN-00170, Finland

    MARJA SORSA

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  1. TERHI KULJUKKA-RABB
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Correspondence to KIMMO PELTONEN.

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KULJUKKA-RABB, T., NYLUND, L., VAARANRINTA, R. et al. The effect of relevant genotypes on PAH exposure-related biomarkers. J Expo Sci Environ Epidemiol 12, 81–91 (2002). https://doi.org/10.1038/sj.jea.7500204

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