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  • Title: Arsenite-induced nitric oxide generation is cell cycle-dependent and aberrant in NBS cells.
    Author: Yuan SS, Hou MF, Chang HL, Chan TF, Wu YH, Wu YC, Su JH.
    Journal: Toxicol In Vitro; 2003 Apr; 17(2):139-43. PubMed ID: 12650666.
    Abstract:
    Exposure to arsenic has been reported to cause DNA damage and eventually the occurrence of bladder, lung and skin cancers. A previous report has demonstrated that arsenite-induced phosphorylation of Mre11, a protein involved in the repair of DNA double strand breaks (DSBs), is M phase-dependent and requires the Nijmegen breakage syndrome (NBS) protein, NBS1 [DNA Repair 1 (2002) 137]. Furthermore, arsenite treatment arrests cells at the M phase and the cells eventually go through apoptosis [Biochemical Pharmacology 60 (2000) 771]. Here we demonstrate that arsenite treatment enhances the generation of nitric oxide (NO), and that the enhanced NO generation is dominant at the G2/M phase. Arsenite-induced NO generation is impaired in DSB repair-defective NBS cells, but not in NBS1-reconstituted NBS cells, suggesting NBS1 is required for effective NO generation. In summary, our study showed, for the first time, that arsenite-induced NO generation is cell-cycle- and NBS1-dependent.
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