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 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.

Association of GSTM1 and GSTT1 with ageing in auto repair shop workers

“…The increase of Comet tail length, MN frequency (Heuser et al, 2007) and shortening telomere length (Nordfjall et al, 2005;Njajou et al, 2007;Hewakapuge et al, 2008) resulting from genetic damages and DNA lesions could be considered as ageing biomarkers. Taking together, the effects of polymorphisms and ageing on the background level of the biomarkers showed the relative effect of lack of GSTT1 (Ada et al, 2007) and GSTM1 on early ageing. This could be attributed to the workers' ancestries and inheritance of unfavorable versions of genes, which increase the effects of reactive metabolites to the environmental mutagens (Laffon et al, 2002).…”

Effect of the GSTM1 genotype on the biomarkers of exposure to polycyclic aromatic hydrocarbons: Meta-analysis

“…After reviewing the full texts, we only included articles that used HPLC for detecting 1-OHP. Eleven studies were finally included in the meta-analysis [35][36][37][38][39][40][41][42][43][44][45]. Table 1 lists these studies and their main features.…”

Cytogenetic Damage in Turkish Coke Oven Workers Exposed to Polycyclic Aromatic Hydrocarbons: Association with CYP1A1, CYP1B1, EPHX1, GSTM1, GSTT1, and GSTP1 Gene Polymorphisms

“…All study subjects were involved in our previous studies (10,19). Participation in this research was voluntary and all subjects were informed about the aims of the study.…”

“…Post shift urine samples were collected in a PVC container without preservatives and kept at -20 °C until analysis, as described in our earlier study (10).…”