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Abstract: Olaquindox, a synthetic antimicrobial compound, is widely used in China as feed additive for growth promotion. However, it is a mutagen with its functional mechanism yet to be unclear. The purpose of this study was to investigate the genotoxic effects of olaquindox in human hepatoma G2 (HepG2) cells and to determine whether the oxidative DNA damage participated in the mechanism of olaquindox toxicity. The results of cell survival assay revealed that the HepG2 cells viabilities were significantly inhibited by olaquindox in a dose- and time-dependent manner. The cytokinesis-block micronucleus (CBMN) assay demonstrated a clear dose–response relationship between olaquindox treatments and micronucleus (MN) frequencies. Moreover, marked increases of DNA fragment migration were observed in the single cell gel electrophoresis (SCGE) assay. These data suggest that olaquindox treatment produced serious chromosome damage and DNA damage in HepG2 cells. To elucidate the possible oxidative DNA damage mechanism of olaquindox genotoxic activity, the levels of the intracellular reactive oxygen species (ROS) and the formation of 8-hydroxydeoxyguanosine (8-OHdG) were detected. The results showed that olaquindox induced the increased levels of ROS and 8-OHdG in HepG2 cells. Considering all the results, it is inferred that olaquindox exerts genotoxic effects in HepG2 cells probably through the ROS-induced oxidative DNA damage. [Copyright &y& Elsevier]

Polycyclic aromatic hydrocarbons (PAH) are well-known to be carcinogenic and the mechanisms that it contributes to oxidative DNA damage and aryl hydrocarbon receptor (AhR)-dependent induction are also well understood. However, little is known about the associations between PAH exposure, AhR expression, and oxidative DNA damage. We investigated their associations of AhR expression and oxidative DNA damage related to PAH exposure among 310 workers from a coke-oven plant in China. Urine biomarkers of PAH exposure (2-hydroxynaphthalene, 2-NAP; 2-hydroxyfluorene, 2-FLU; 9-hydroxyphenanthren, 9-PHE; and 1-hydroxypyrene, 1-OHP) and a marker of oxidative damage (8-hydroxy- 2'- deoxyguanosine, 8-OHdG) were measured by high performance liquid chromatography. AhR expression in venous blood was measured by reverse transcription -polymerase chain reaction. The results showed that increasing levels of urinary 1-OHP was positively associated with high 8-OHdG (OR (95% CI) was 4.01 (1.41-11.45) for 4th quartile, compared with 1st quartile, P for trend = 0.013). The similar associations were also found between urinary 1-OHP and high-AhR expressions (4th vs. 1st quartile = 3.50, 95% CI: 1.24-9.87, P for trend = 0.029). A significant association between AhR expression and high 8-OHdG was also found (4th vs. 1st quartile = 2.44, 95% CI: 1.05-5.70, P for trend = 0.027). In addition, mediation analysis showed the AhR expression could explain 35.9% of the association of oxidative DNA damage related to PAH exposure. Our findings implicated that the association between PAH exposure and oxidative DNA damage may be mediated by AhR expression among Chinese occupational workers., (Copyright © 2018 Elsevier Ltd. All rights reserved.)