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

Abstract

Genetic polymorphisms of xenobiotic metabolizing enzymes have beenassociated with cancer risk. We evaluated the influences of geneticpolymorphisms of polycyclic aromatic hydrocarbon (PAH) metabolizingenzymes on urinary 1-hydroxypyrene (1-OHP) excretion in Turkish cokeoven workers. Urinary 1-OHP was analyzed by HPLC after enzymatichydrolysis. Lymphocyte DNA was used for PCR-based genotyping ofcytochrome P450 (CYP) polymorphisms (CYP1A1 and CYP1B1) and glutathioneS-transferases (GST) polymorphisms (GSTM1, GSTT1 and GSTP1). The meanurinary 1-OHP levels of coke oven workers were significantly higher thanthat of controls. No significant difference was detected in the meanurinary 1-OHP levels of smokers and non-smokers either for coke ovenworkers or controls. Genetic polymorphisms of the CYPs and GSTs studiedhad no significant influence on 1-OHP excretion in coke oven workers,but in the control group the urinary 1-OHP levels of individualscarrying the GSTT1 genotype were significantly higher than those ofindividuals carrying GSTT1 + genotype, The duration of occupationalexposure and metabolic genotype for GSTT1 were the significantpredictors of urinary 1-OHP levels. The control individuals carryingcombined GSTM1-/GSTT1-genotypes also had significantly higher levels ofurinary 1-OHP than those of individuals carrying GSTM1+/GSTTI+,GSTM1-/GSTT1+, and GSTM1+/GSTT1-genotypes. These results indicate thaturinary 1-OHP is a sensitive indicator of recent human exposure to PAHsand that genetic polymerphism of GSTT1 may also to some extent reflectthe interindividual variation in susceptibility to PAHs only at low PAHexposure.