TY - JOUR
T1 - DNA damage and repair, oxidative stress and metabolism biomarker responses in lungs of rats exposed to ambient atmospheric 1-nitropyrene
AU - Li, Ruijin
AU - Zhao, Lifang
AU - Zhang, Li
AU - Chen, Minghui
AU - Dong, Chuan
AU - CAI, Zongwei
N1 - Funding Information:
This research was supported by the National Natural Science Foundation of China (No. 91543202 and 21575084), HKBU Strategic Development Fund (15-1012-P04), Nature Science Foundation of Shanxi Province in China (No. 2014011036-2), and Foundation of Educational Committee of Shanxi Province in China (No. 2014110).
PY - 2017/9
Y1 - 2017/9
N2 - 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 × 10−5, 4.0 × 10−5 and 1.6 × 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 × 10−5 and 1.6 × 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.
AB - 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 × 10−5, 4.0 × 10−5 and 1.6 × 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 × 10−5 and 1.6 × 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.
KW - 1-Nitropyrene
KW - DNA damage and repair
KW - Metabolic enzymes
KW - Oxidative stress
KW - Rat lungs
UR - http://www.scopus.com/inward/record.url?scp=85021414562&partnerID=8YFLogxK
U2 - 10.1016/j.etap.2017.06.009
DO - 10.1016/j.etap.2017.06.009
M3 - Journal article
C2 - 28668703
AN - SCOPUS:85021414562
SN - 1382-6689
VL - 54
SP - 14
EP - 20
JO - Environmental Toxicology and Pharmacology
JF - Environmental Toxicology and Pharmacology
ER -