Primary DNA damage and genetic polymorphisms for CYP1A1, EPHX and GSTM1 in workers at a graphite electrode manufacturing plant.
BACKGROUND
The results of a cross-sectional study aimed to evaluate whether genetic polymorphisms (biomarkers of susceptibility) for CYP1A1, EPHX and GSTM1 genes that affect polycyclic aromatic hydrocarbons (PAH) activation and detoxification might influence the extent of primary DNA damage (biomarker of biologically effective dose) in PAH exposed workers are presented. PAH-exposure of the study populations was assessed by determining the concentration of 1-hydroxypyrene (1OHP) in urine samples (biomarker of exposure dose).


METHODS
The exposed group consisted of workers (n = 109) at a graphite electrode manufacturing plant, occupationally exposed to PAH. Urinary 1OHP was measured by HPLC. Primary DNA damage was evaluated by the alkaline comet assay in peripheral blood leukocytes. Genetic polymorphisms for CYP1A1, EPHX and GSTM1 were determined by PCR or PCR/RFLP analysis.


RESULTS
1OHP and primary DNA damage were significantly higher in electrode workers compared to reference subjects. Moreover, categorization of subjects as normal or outlier highlighted an increased genotoxic risk OR = 2.59 (CI95% 1.32-5.05) associated to exposure to PAH. Polymorphisms in EPHX exons 3 and 4 was associated to higher urinary concentrations of 1OHP, whereas none of the genotypes analyzed (CYP1A1, EPHX, and GSTM1) had any significant influence on primary DNA damage as evaluated by the comet assay.


CONCLUSIONS
The outcomes of the present study show that molecular epidemiology approaches (i.e. cross-sectional studies of genotoxicity biomarkers) can play a role in identifying common genetic risk factors, also attempting to associate the effects with measured exposure data. Moreover, categorization of subjects as normal or outlier allowed the evaluation of the association between occupational exposure to PAH and DNA damage highlighting an increased genotoxic risk.
Moretti
Massimo
M
Department of Medical-Surgical Specialities and Public Health, University of Perugia, Via del Giochetto, 06122 Perugia, Italy. massimo.moretti@unipg.it
Dell'Omo
Marco
M
Villarini
Milena
M
Pastorelli
Roberta
R
Muzi
Giacomo
G
Airoldi
Luisa
L
Pasquini
Rossana
R
D000328:Adult; D015415:Biomarkers; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics*; D020552:Comet Assay; D003430:Cross-Sectional Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004249:DNA Damage; D004566:Electrodes; D004851:Epoxide Hydrolases / Q000235:genetics*; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006108:Graphite; D006801:Humans; D007558:Italy; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008420:Manufactured Materials; D054526:Men's Health; D016273:Occupational Exposure; D010944:Plants; D011110:Polymorphism, Genetic; D011721:Pyrenes / Q000493:pharmacokinetics / Q000633:toxicity*; D017132:Workplace
D015415:Biomarkers; D002786:Cholesterol Side-Chain Cleavage Enzyme; D019363:Cytochrome P-450 CYP1A1; D004851:Epoxide Hydrolases; D005982:Glutathione Transferase; D006108:Graphite; D011721:Pyrenes; C033146:1-hydroxypyrene