Arsenite-induced nitric oxide generation is cell cycle-dependent and aberrant in NBS cells.
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.
Yuan
S S
SS
Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 807, Republic of China.
Hou
M F
MF
Chang
H L
HL
Chan
T F
TF
Wu
Y H
YH
Wu
Y C
YC
Su
J H
JH
D018053:Arsenites / Q000633:toxicity*; D018797:Cell Cycle Proteins / Q000378:metabolism* / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D000076228:MRE11 Homologue Protein; D008938:Mitosis / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000378:metabolism
D018053:Arsenites; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; C112156:NBN protein, human; D009687:Nuclear Proteins; D009569:Nitric Oxide; D000076228:MRE11 Homologue Protein; C015001:arsenite