Primary DNA damage and genetic polymorphisms for CYP1A1, EPHX and GSTM1 in workers at a graphite electrode manufacturing plant

Massimo Moretti, Marco Dell'Omo, Milena Villarini, Roberta Pastorelli, Giacomo Muzi, Luisa Airoldi, Rossana Pasquini

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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. Conclusion. 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.

Original languageEnglish
Article number270
JournalBMC Public Health
Volume7
DOIs
Publication statusPublished - 2007

Fingerprint

Cytochrome P-450 CYP1A1
Graphite
Polycyclic Aromatic Hydrocarbons
Genetic Polymorphisms
DNA Damage
Electrodes
Biomarkers
Comet Assay
Cross-Sectional Studies
Polymerase Chain Reaction
Molecular Epidemiology
Occupational Exposure
Restriction Fragment Length Polymorphisms
Manufacturing and Industrial Facilities
Exons
Leukocytes
Genotype
High Pressure Liquid Chromatography
Outcome Assessment (Health Care)
Urine

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health

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Primary DNA damage and genetic polymorphisms for CYP1A1, EPHX and GSTM1 in workers at a graphite electrode manufacturing plant. / Moretti, Massimo; Dell'Omo, Marco; Villarini, Milena; Pastorelli, Roberta; Muzi, Giacomo; Airoldi, Luisa; Pasquini, Rossana.

In: BMC Public Health, Vol. 7, 270, 2007.

Research output: Contribution to journalArticle

Moretti, Massimo ; Dell'Omo, Marco ; Villarini, Milena ; Pastorelli, Roberta ; Muzi, Giacomo ; Airoldi, Luisa ; Pasquini, Rossana. / Primary DNA damage and genetic polymorphisms for CYP1A1, EPHX and GSTM1 in workers at a graphite electrode manufacturing plant. In: BMC Public Health. 2007 ; Vol. 7.
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