Journal
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
Volume 54, Issue -, Pages 14-20Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.etap.2017.06.009
Keywords
1-Nitropyrene; DNA damage and repair; Rat lungs; Oxidative stress; Metabolic enzymes
Funding
- National Natural Science Foundation of China [91543202, 21575084]
- HKBU Strategic Development Fund [15-1012-P04]
- Nature Science Foundation of Shanxi Province in China [2014011036-2]
- Foundation of Educational Committee of Shanxi Province in China [2014110]
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1-Nitropyrene (1-NP) is a mutagenic and carcinogenic pollutant very widespread in the environment. However, the relative investigations on genotoxicity, oxidative stress and metabolic enzymes in lungs of mammalian caused by 1-NP have not been fully established. In this study, the 1-NP solutions at 3 dosages (1.0 x 10(-5), 4.0 x 10(-5) and 1.6 x 10(-4) mg/kg body weight) were respectively given to rats by the intratracheal instillation. The responses of 1-NP on DNA damage and repair, oxidative stress and metabolism biomarkers in rat lungs after exposure to 1-NP were measured. The results showed 1-NP at three dosages induced obvious DNA strand breaks, 8-OH-dG formation and DNA-protein cross-link in rat lungs compared with the control. Higher dosage 1-NP (4.0 x 10(-5) and 1.6 x 10(-4) mg/kg body weight) greatly activated DNA repair gene OGG1 and inhibited MTH1 and XRCC1 expressions, and they significantly elevated the levels of GADD153, heme oxygenase-1 and malondialdehyde and decreased SOD activity, accompanied by the increases of CYP450, CYP1A1, CYP1A2 and GST levels. These results suggested the genotoxicity of 1-NP might rely on 1-NP-caused DNA damage and its combined effects on the suppression of DNA repair and the enhancement of oxidative stress and metabolic enzyme activity.
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