1. ¹Institute of Occupational Health, FIN-00250 Helsinki, Finland
2. ²National Product Control Agency for Welfare and Health, FIN-00530 Helsinki, Finland
3. ³Karolinska Institute and National Institute for Working Life, Stockholm, Sweden
4. ⁴Department of Epidemiology and Biostatistics, FIOH, FIN-00250 Helsinki, Finland
5. ⁵Institute of Experimental and Clinical Medicine, Tallinn, Estonia
6. ⁶Ministry of Education, FIN-00170 Helsinki, Finland

Correspondence: Dr. Kimmo Peltonen, Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, FIN-00250 Helsinki, Finland. Tel.: +358-9-4747-2216. E-mail: kimmo.peltonen@ttl.fi

Received 28 November 2001.

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.