Abstract

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.

Highlights

  • Polycyclic aromatic hydrocarbons (PAHs) are present in the environment when coal is pyrolysed into coke, because of which coke oven workers are at a high risk of exposure to polycyclic aromatic hydrocarbon (PAH) (Wu et al, 1998; Kuljukka-Rabb et al, 2002)

  • In the study described in this paper, we evaluate the influence of polymorphisms in enzymes involved in PAH metabolism on the urinary excretion of 1-OHP of Turkish coke oven workers possibly exposed to PAH and controls who had no occupational exposure to PAH

  • We investigated whether the CYP1A1, CYP1B1, GSTM1, GSTP1 and GSTT1 polymorphisms have any influence on urinary 1-OHP levels of Turkish coke oven workers, possibly exposed to polycyclic aromatic hydrocarbons (PAHs), and controls from the same factory who should not have had occupational exposure to PAHs

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Summary

Introduction

Polycyclic aromatic hydrocarbons (PAHs) are present in the environment when coal is pyrolysed into coke, because of which coke oven workers are at a high risk of exposure to PAHs (Wu et al, 1998; Kuljukka-Rabb et al, 2002). In the study described in this paper, we evaluate the influence of polymorphisms in enzymes involved in PAH metabolism on the urinary excretion of 1-OHP of Turkish coke oven workers possibly exposed to PAH and controls who had no occupational exposure to PAH.

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