一氧化氮供体硝普钠致DNA单链断裂的试验研究

Studies on DNA Single Strand Breaks Induced by Sodium Nitroprusside nitric Oxide Donor

目的 研究一氧化氮供体硝普钠（ＳＮＰ） 对ＤＮＡ 单链断裂的影响。方法 用改进的方法分离制备小鼠脏器单细胞悬液，用碱性单细胞凝胶电泳法检测ＳＮＰ 处理后体内外细胞ＤＮＡ 损伤情况。结果 ０ ．５ ～２ ．０ μｍｏｌ／ｍｌＳＮＰ（ ＋ Ｓ９） 处理１ 小时可诱发ｇ１２ 细胞ＤＮＡ 单链断裂。腹腔注射０ ．６７ ～６ ．０ ｍｇ／ｋｇ ＳＮＰ可诱发小鼠体内脾细胞、胸腺细胞和腹腔巨噬细胞的ＤＮＡ 单链断裂，但未观察到对肝、肾和肺细胞的影响。结论 一氧化氮可致体内外某些细胞ＤＮＡ 单链断裂。小鼠体内不同脏器细胞对一氧化氮的易感性不同，脾细胞、胸腺细胞和巨噬细胞可能是一氧化氮重要的靶细胞。

Objective To study the effect of sodium nitroprusside(SNP), a nitric oxide(NO) donor, on DNA single strand breaks (SSBs). Methods A modified method was used to isolate and prepare the single cell suspension from the organs of mice. Alkaline single cell gel electrophoresis (SCGE) was performed to examine DNA damage of the cells treated by SNP in vivo and in vitro . Results Treatment with 0.5～2.0 μmol/ml of SNP with S 9 for 1 h induced a concentration dependent increase in DNA SSBs in g12 cells. Significant increase in DNA migration and comet frequency in the spleen,thymus and peritoneal macrophage were induced after intraperitoneal injection of SNP at a dose of 0.67～6.0 mg/kg. No obvious increase in DNA single strand breaks was observed in the liver,kidney and lung of the mice with same treatment. Conclusion DNA SSBs could be induced by NO in some cells in vivo and in vitro . There was difference in sensitivity of various organs in the mice to NO. Cells of spleen and thymus and macrophage may be the important target cells of NO.