title: GSTM1 null genotype as a risk factor for anti-BPDE-DNA adduct formation in mononuclear white blood cells of coke-oven workers.
abstract: The influence of the genetic deletion polymorphism of glutathione S-transferase micro 1 (GSTM1 *0/*0) on levels of anti (+/-)-r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE-DNA) adduct in the peripheral blood lymphocyte plus monocyte fraction (LMF) of coke-oven workers was investigated. A total of 95 male Polish coke-oven workers (60% current smokers) from two different plants comprised the sample population. Polycyclic aromatic hydrocarbons (PAH) exposure was assessed by means of the individual post-shift urinary excretion of 1-pyrenol (mean +/- S.D.: 6.93 +/- 7.20 micromol/mol creatinine; 70% of the subjects exceeded the proposed biological exposure index (BEI) 2.28 micromol/mol creatinine). Anti-BPDE-DNA adduct levels were detected by high performance liquid chromatography (HPLC)/fluorescence analysis of the anti-BPDE tetrol I-1 released after acid hydrolysis of DNA samples. Genotypes were determined by polymerase chain reaction (PCR) on the genomic DNA of each subject. Coke-oven workers without active GSTM1 (GSTM1 *0/*0, 33%) had significantly higher adduct levels than those with active GSTM1 (GSTM1*1/*1 and *1/*0) (5.90 +/- 5.59 versus 3.25 +/- 2.01 adducts/10(8) bases, Mann-Whitney U-test, z = 2.53, P = 0.011), PAH exposure in the two subgroups being similar (7.06 +/- 6.83 versus 6.67 +/- 8.00 1-pyrenol micromol/mol creatinine). The highest number of GSTM1 null subjects (12/23, 39%) belonged to the quartile with the highest adduct levels (i.e., >4.67 adducts/10(8) nucleotides). That is, coke-oven workers with GSTM1 *0/*0 genotype had a significantly higher risk of having high adduct levels than individuals with active GSTM1 genotype (Fisher exact test P = 0.0355; odds ratio (OR) = 4.145, 95% CI 1.0-18.8). Multiple linear regression analysis showed that the increase in anti-BPDE-DNA adduct levels in LMF was significantly related to the high occupational exposure to PAHs (benzo[a]pyrene (BaP)) of coke-oven workers (t = 3.087, P < 0.01) and to the lack of GSTM1 activity (t = 3.512, P < 0.001), rather than to the two other confounding factors of PAH intake, i.e. charcoal-broiled meat consumption and smoking habits. In conclusion, our results indicate the clear influence of the GSTM1 detoxifying genotype on anti-BPDE-DNA adduct formation in the LMF of coke-oven workers. This is invaluable for future environmental-occupational studies using this biomarker of PAH exposure.
authors.affiliation: Occupational Health Section, Department of Environmental and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy.
authors.forename: Sofia
authors.initials: S
authors.lastname: Pavanello
authors.forename: Ewa
authors.initials: E
authors.lastname: Siwinska
authors.forename: Danuta
authors.initials: D
authors.lastname: Mielzynska
authors.forename: Erminio
authors.initials: E
authors.lastname: Clonfero
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D000328:Adult; D002851:Chromatography, High Pressure Liquid; D003077:Coke; D018736:DNA Adducts / Q000097:blood*; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology / Q000378:metabolism*; D016273:Occupational Exposure; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D013050:Spectrometry, Fluorescence
chemical_list: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D003077:Coke; D018736:DNA Adducts; D005982:Glutathione Transferase; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA