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

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 ?H2AX, 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. [ABSTRACT FROM AUTHOR]