Effect of nitric oxide on γ-ray-induced micronucleus frequency in RAW264.7 cells

Sachiko Tokuzumi, Mayumi Hori, Manami Monobe, Yoshio Hosoi, Shuji Kojima

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The effect of low-dose nitric oxide (NO) on γ-ray-induced micronucleus (MN) frequency was investigated in RAW264.7 cells. Treatment of RAW264.7 cells with 0.25 mM sodium nitroprusside (SNP), a chemical NO donor, reduced the frequency of micronuclei induced by 5 Gy γ rays by 43 to 45% between 3 and 12 h post-treatment. This effect was blocked by carboxy-PTIO, suggesting that NO may play a role in the reduction of radiation-induced MN frequency. To examine possible mechanisms underlying this effect, we first looked at changes in the antioxidant system after SNP treatment. A significant increase in intracellular glutathione (GSH) was seen in SNP-treated cells between 3 and 12 h post-treatment. Depletion of GSH with buthionine sulfoximine (BSO) increased the γ-ray-induced increase in MN frequency. Detailed studies using various inducers of intracellular GSH suggested that GSH induction has a partial role in the reducing effect of NO on the γ-ray-induced MN frequency. Next, the effect of NO on DNA repair and replication systems was examined. Wortmannin, an inhibitor of DNA-dependent protein kinase (DNA-PK), dose-dependently inhibited the reducing effect of NO, while caffeine, an inhibitor of ATM kinase and ATR kinase, did not. DNA-PK activity was increased by NO treatment. Etoposide, a topoisomerase II inhibitor, dose-dependently blocked the effect of NO in reducing the γ-ray-induced MN frequency. These results suggest that the mechanisms of the effect of NO on the γ-ray-induced MN frequency include elevation of GSH and up-regulation of DNA-PK activity for repairing double-strand breaks. NO may act as a signal for repair systems, e.g. for nonhomologous recombination and for the replication system in S phase, to reduce the MN frequency.

Original languageEnglish
Pages (from-to)723-732
Number of pages10
JournalRadiation Research
Volume164
Issue number6
DOIs
Publication statusPublished - 2005 Dec 1
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

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