Association between urinary 1-hydroxypyrene and genotoxic effects in coke oven workers

Abstract

Aims: To investigate whether current occupational exposure of coke oven workers to polycyclic aromatic hydrocarbons (PAHs) results in genotoxic effects measured in peripheral blood lymphocytes and whether these biomarkers are associated with the biomarkers of exposure. Methods: Blood and urine samples were collected immediately after a shift at the end of a working week from 50 coke oven workers and 50 control workers not exposed to PAHs. Methods included: (1) biomarkers of exposure: urinary 1-hydroxypyrene (HpU), urinary mutagenicity by the plate Salmonella test with strains TA98 and YG1024 after metabolic activation, expressed as mutagenic rate (MR98 and MR1024, respectively), urinary cotinine; and (2) biomarkers of biological effects in peripheral blood lymphocytes (PBL): sister chromatid exchanges (SCE/cell), cells of high frequency of SCE (% HFC), micronuclei (MN/1000 cells), chromosomal aberrations (CA/100 cells), and DNA damage by the Comet assay. Results: Occupational exposure to PAH resulted in significantly increased levels of HpU and mutagenic effect of urine. Median values of these biomarkers in coke oven workers were: 9.0 mmol/mol creatinine for HpU, 2.7 for MR98, and 8.2 for MR1024, compared to the controls: HpU = 0.6 mmol/mol creatinine, MR98 = 1.2, and MR1024 = 5.5. Occupational exposure caused significant induction of SCE, HFC, and MN in coke oven workers: median SCE = 5.9, HFC = 12.0%, MN = 6.0 compared to the controls: 3.9, 5.0%, and 3.0, respectively. No effect of occupational exposure was found in relation to CA and DNA damage measured with the Comet assay. HpU concentration was positively associated with SCE and HFC. The concentration of urinary 1-hydroxypyrene corresponding to a 5% probability of increased SCE was 1.0 mmol/mol creatinine. Conclusions: The occupational exposure to PAHs resulted in measurable biological effects (SCE, HFC, MN). In coke oven workers an increased level of SCE was not observed below the level of 1.0 mmol HpU/ mol creatinine.

Synergistic Increase of Oxidative Stress and Tumor Markers in PAH-Exposed Workers

“…The PAHs exposure of coke-oven workers in the present study was similar with that in Siwińska et al's and in Zhang's study conducted in coke oven workers and much higher than that reported by Pavanello et al in CMBN assay in coke oven workers (Zhang et al, 2001;Siwińska et al, 2004;Pavanello et al, 2008). Though the length of exposure is not, therefore, the only risk factor (Pavanello et al, 2008).…”

Global and gene‐specific promoter methylation changes are related to anti‐B[a]PDE‐DNA adduct levels and influence micronuclei levels in polycyclic aromatic hydrocarbon‐exposed individuals

“…At the same time as urine was collected, blood samples were taken and placed in EDTAcontaining tubes (20 ml) and evacuated heparin-containing tubes (10 ml) for adduct and MN analysis, as previously described. 25,30 At the Institute of Occupational Medicine and Environmental Health in Sosnowiec: (i) PBL cultures for MN detection were prepared and MN analyses performed; (ii) PBLs for adduct analyses were isolated in Ficoll separating solution (Seromed, Berlin, Germany) within 4 hr after blood collection and kept frozen at 280°C, until they were sent to the Department of Environmental Medicine and Public Health in Padova (Italy), where DNA was extracted. Data on other possible elevated nonoccupational PAH exposure (diet, environment) and consumption of fruit and vegetables were collected by means of a questionnaire, as previously described 23,24 (i.e., high dietary intake of PAHs was the consumption of charcoaled meat (PAH-rich meals) more than once a week; indoor and environmental exposure to PAHs was the use of wood or coal to heat the home, and an index of location of residence that included intense local traffic and presence of industries in the residential area).…”

“…24 MN analysis was performed on coded slides scored by light microscopy at 4003 magnification, as previously described. 30 To exclude artefacts, the identification of MN was confirmed at 1,0003 magnification in 10% of samples. The scoring of bi-, tri-and tetranucleate cells and MN was done and the cytokinesis block proliferation index was calculated as being equal in both groups (p 5 0.599).…”

PAH biomarkers for human health risk assessment: a review of the state-of-the-art

“…In cases of complex mixtures, more than one biomarker should be considered to ensure adequate evaluation. 1-hydroxypyrene is the most widely used metabolite in PAH exposure, since pyrene is one of the most abundant hydrocarbons in all PAH mixtures and has as its principal metabolite 1-hydroxypyrene formed in mammals 3,16,17 , thus representing a sensitive biomarker of exposure, recommended by various authors as the most relevant parameter in estimates of individual exposure to PAH 1,17,18,19,20,21 . Smoking is monitored with cotinine (a hydroxyl metabolite of nicotine), which allows controlling this intervening variable in studies on environmental PAH exposure 3,15 .…”