Journal Article

Analysis of 8-oxo-7,8-dihydro-2′-deoxyguanosine and DNA strand breaks in white blood cells of occupationally exposed workers: comparison with ambient monitoring, urinary metabolites and enzyme polymorphisms

B. Marczynski, H.-P. Rihs, B. Rossbach, J. Hölzer, J. Angerer, M. Scherenberg, G. Hoffmann, T. Brüning and M. Wilhelm

in Carcinogenesis

Volume 23, issue 2, pages 273-281
Published in print February 2002 | ISSN: 0143-3334
Published online February 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.2.273
Analysis of 8-oxo-7,8-dihydro-2′-deoxyguanosine and DNA strand breaks in white blood cells of occupationally exposed workers: comparison with ambient monitoring, urinary metabolites and enzyme polymorphisms

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The relationship between biomarkers of effect (8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo, HPLC system) and tail extent moment (comet assay)), markers of external and internal exposure, and biomarkers of susceptibility was evaluated for coke-oven and graphite-electrode-producing plant workers exposed to polycyclic aromatic hydrocarbons (PAHs). Mean 8-oxodGuo levels in white blood cells (WBC) of exposed workers were between 1.38 times (coke-oven, n = 20; P < 0.01) and 2.15 times (graphite-electrode-producing plant, n = 30; P < 0.01) higher than levels found in control samples (mean ± SD 0.52 ± 0.16 8-oxodGuo/105 dGuo, n = 47). The mean tail extent moment in lymphocytes was 1.38 times higher for coke-oven workers (n = 19; P = 0.09) and 3.13 times higher for graphite-electrode-producing plant workers (n = 29; P < 0.01) when compared with controls (mean ± SD 2.54 ± 0.68, n = 32). Elevated tail extent moments (>3.73) were found in the majority (84%) of PAH-exposed workers showing increased DNA adduct levels (>0.78 8-oxodGuo/105 dGuo). However, no association (P > 0.05) was found between DNA damage (8-oxodGuo/105 dGuo or tail extent moment) in WBC of all PAH-exposed workers and either benzo[a]pyrene levels or the sum of 16 PAH levels in the air at work place. Furthermore, no relation (P > 0.05) could be established between DNA damage in WBC and biomarkers of internal exposure (1-hydroxypyrene (1-OHP) and sum of five hydroxyphenanthrenes (OHPHs)). Higher exposure to airborne pyrene and phenanthrene led to increasing concentrations of the metabolites 1-OHP (P < 0.01) and the sum of five OHPHs (P < 0.01) in the urine of PAH-exposed workers. The polymorphisms of genes CYP1A1, GSTM1, GSTT1 and GSTP1 (biomarkers of susceptibility) showed no association with biomarkers of effect. In conclusion, both biomarkers of effect may be appropriate for further surveillance studies of workers under PAH exposure.

Keywords: acn, acetonitrile; AP, apurinic/apyrimidinic; B[a]P, benzo[a] pyrene; BPDE, benzo[a]pyrene diolepoxide; CYP, cytochrome P450; GST, glutathione S-transferase; 1-OHP, 1-hydroxypyrene; OHPH, hydroxyphenanthrene; 8-oxodGuo, 8-oxo-7,8-dihydro-2′-deoxyguanosine; PAH, polycyclic aromatic hydrocarbons; PCR–RFLP, polymerase chain reaction–restriction fragment lengths polymorphism; ROS, reactive oxygen species; rS, Spearman rank correlation coefficient; LOD, limit of detection; SD, standard deviation; WBC, white blood cells; XAD-2, polystyrene/divinyl benzene-based polymer

Journal Article.  8251 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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