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Title: Polychlorinated biphenyl quinone induces oxidative DNA damage and repair responses: The activations of NHEJ, BER and NER via ATM-p53 signaling axis

Abstract

Our previous studies demonstrated that polychlorinated biphenyl (PCB) quinone induced oxidative DNA damage in HepG2 cells. To promote genomic integrity, DNA damage response (DDR) coordinates cell-cycle transitions, DNA repair and apoptosis. PCB quinone-induced cell cycle arrest and apoptosis have been documented, however, whether PCB quinone insult induce DNA repair signaling is still unknown. In this study, we identified the activation of DDR and corresponding signaling events in HepG2 cells upon the exposure to a synthetic PCB quinone, PCB29-pQ. Our data illustrated that PCB29-pQ induces the phosphorylation of p53, which was mediated by ataxia telangiectasia mutated (ATM) protein kinase. The observed phosphorylated histone H2AX (γ-H2AX) foci and the elevation of 8-hydroxy-2′-deoxyguanosine (8-OHdG) indicated that DDR was stimulated by PCB29-pQ treatment. Additionally, we found PCB29-pQ activates non-homologous end joining (NHEJ), base excision repair (BER) and nucleotide excision repair (NER) signalings. However, these repair pathways are not error-free processes and aberrant repair of DNA damage may cause the potential risk of carcinogenesis and mutagenesis. - Highlights: • Polychlorinated biphenyl quinone induces oxidative DNA damage in HepG2 cells. • The elevation of γ-H2AX and 8-OHdG indicates the activation of DNA damage response. • ATM-p53 signaling acts as the DNA damage sensor and effector. •more » Polychlorinated biphenyl quinone activates NHEJ, BER and NER signalings.« less

Authors:
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Publication Date:
OSTI Identifier:
22465776
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 286; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADP; APOPTOSIS; BENZOQUINONES; BIOLOGICAL PATHWAYS; CARCINOGENESIS; CARCINOMAS; CELL CYCLE; DNA; DNA DAMAGES; EXCISION REPAIR; GENE RECOMBINATION; HAZARDS; LIVER; MUTAGENESIS; OXIDATION; PHOSPHORYLATION; POLYCHLORINATED BIPHENYLS; SENSORS; X RADIATION

Citation Formats

Dong, Hui, Shi, Qiong, Song, Xiufang, Fu, Juanli, Hu, Lihua, Xu, Demei, Su, Chuanyang, Xia, Xiaomin, Song, Erqun, and Song, Yang. Polychlorinated biphenyl quinone induces oxidative DNA damage and repair responses: The activations of NHEJ, BER and NER via ATM-p53 signaling axis. United States: N. p., 2015. Web. doi:10.1016/J.TAAP.2015.03.017.
Dong, Hui, Shi, Qiong, Song, Xiufang, Fu, Juanli, Hu, Lihua, Xu, Demei, Su, Chuanyang, Xia, Xiaomin, Song, Erqun, & Song, Yang. Polychlorinated biphenyl quinone induces oxidative DNA damage and repair responses: The activations of NHEJ, BER and NER via ATM-p53 signaling axis. United States. https://doi.org/10.1016/J.TAAP.2015.03.017
Dong, Hui, Shi, Qiong, Song, Xiufang, Fu, Juanli, Hu, Lihua, Xu, Demei, Su, Chuanyang, Xia, Xiaomin, Song, Erqun, and Song, Yang. 2015. "Polychlorinated biphenyl quinone induces oxidative DNA damage and repair responses: The activations of NHEJ, BER and NER via ATM-p53 signaling axis". United States. https://doi.org/10.1016/J.TAAP.2015.03.017.
@article{osti_22465776,
title = {Polychlorinated biphenyl quinone induces oxidative DNA damage and repair responses: The activations of NHEJ, BER and NER via ATM-p53 signaling axis},
author = {Dong, Hui and Shi, Qiong and Song, Xiufang and Fu, Juanli and Hu, Lihua and Xu, Demei and Su, Chuanyang and Xia, Xiaomin and Song, Erqun and Song, Yang},
abstractNote = {Our previous studies demonstrated that polychlorinated biphenyl (PCB) quinone induced oxidative DNA damage in HepG2 cells. To promote genomic integrity, DNA damage response (DDR) coordinates cell-cycle transitions, DNA repair and apoptosis. PCB quinone-induced cell cycle arrest and apoptosis have been documented, however, whether PCB quinone insult induce DNA repair signaling is still unknown. In this study, we identified the activation of DDR and corresponding signaling events in HepG2 cells upon the exposure to a synthetic PCB quinone, PCB29-pQ. Our data illustrated that PCB29-pQ induces the phosphorylation of p53, which was mediated by ataxia telangiectasia mutated (ATM) protein kinase. The observed phosphorylated histone H2AX (γ-H2AX) foci and the elevation of 8-hydroxy-2′-deoxyguanosine (8-OHdG) indicated that DDR was stimulated by PCB29-pQ treatment. Additionally, we found PCB29-pQ activates non-homologous end joining (NHEJ), base excision repair (BER) and nucleotide excision repair (NER) signalings. However, these repair pathways are not error-free processes and aberrant repair of DNA damage may cause the potential risk of carcinogenesis and mutagenesis. - Highlights: • Polychlorinated biphenyl quinone induces oxidative DNA damage in HepG2 cells. • The elevation of γ-H2AX and 8-OHdG indicates the activation of DNA damage response. • ATM-p53 signaling acts as the DNA damage sensor and effector. • Polychlorinated biphenyl quinone activates NHEJ, BER and NER signalings.},
doi = {10.1016/J.TAAP.2015.03.017},
url = {https://www.osti.gov/biblio/22465776}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 286,
place = {United States},
year = {Wed Jul 01 00:00:00 EDT 2015},
month = {Wed Jul 01 00:00:00 EDT 2015}
}