Nuclear respiratory factor 1 overexpression attenuates anti-benzopyrene‑7,8-diol-9,10-epoxide-induced S-phase arrest of bronchial epithelial cells

Wu,Jing; Wang,Yaning; Wo,Da; Zhang,Lijuan; Li,Jue

doi:10.3892/mmr.2016.5065

Nuclear respiratory factor 1 overexpression attenuates anti-benzopyrene‑7,8-diol-9,10-epoxide-induced S-phase arrest of bronchial epithelial cells

Authors:
- Jing Wu
- Yaning Wang
- Da Wo
- Lijuan Zhang
- Jue Li
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Affiliations: Division of Preventive Medicine, Tongji University School of Medicine, Shanghai 200092, P.R. China
Published online on: March 30, 2016 https://doi.org/10.3892/mmr.2016.5065
Pages: 4372-4378

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Abstract

Nuclear respiratory factor 1 (NRF-1) has important roles in the regulation of several key metabolic genes required for cellular growth and respiration. A previous study by our group indicated that NRF‑1 is involved in mitochondrial dysfunction induced by the environmental pollutant benzo[a]pyrene in the 16HBE human bronchial epithelial cell line. In the present study, it was observed that its genotoxic metabolite, anti‑benzopyrene‑7,8‑diol‑9,10‑epoxide (BPDE), triggered cell cycle arrest in S‑phase in 16HBE cells by activating ataxia-telangiectasia (ATM)/checkpoint kinase (Chk)2 and ATM and Rad3 related (ATR)/Chk1 signaling pathways. NRF‑1 expression was suppressed by BPDE after treatment for 6 h. Flow cytometric analysis revealed that NRF‑1 overexpression attenuated cell cycle arrest in S‑phase induced by BPDE. In line with this result, DNA‑damage checkpoints were activated following NRF‑1 overexpression, as demonstrated by increased phosphorylation of ATM, Chk2 and γH2AX, but not ATR and Chk1, according to western blot analysis. It was therefore indicated that NRF‑1 overexpression attenuated BPDE‑induced S‑phase arrest via the ATM/Chk2 signaling pathway.

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