一氧化氮供体药物硝普钠的遗传毒性的研究  

STUDIES ON GENOTOXICITY OF SODIUM NITROPRUSSIDE (SNP),A DRUG DONOR OF NITRIC OXIDE

作　　者：林慰慈[1,2] 薛宏伟[1,2] 刘胜英[1,2] 何轶勤 付娟玲 周宗灿[1,2] 

机构地区：[1]北京医科大学卫生毒理教研室 [2]北京医科大学预防医学系

出　　处：《癌变．畸变．突变》1997年第4期211-215,共5页Carcinogenesis,Teratogenesis & Mutagenesis

摘　　要：本文以硝普钠（ＳＮＰ）为ＮＯ供体药物，研究慢性升高的ＮＯ对哺乳动物细胞的诱变作用和微核形成的影响。结果ＳＮＰ（２－８ｍＭ，不加或加Ｓ９）处理，均以剂量—反应方式诱发ｇ１２细胞ｇｐｔ位点突变，在最高受试剂量，诱变率分别超过本底１３和２５倍。在处理组还观察到含微核的双核细胞数显著增多。在０．５－４ｍＭ（＋Ｓ９）或２－８ｍＭ（－Ｓ９）ＳＮＰ剂量范围内，双核微核细胞率、微核率及含多微核的双核细胞比率均以剂量—依存方式增加。结果表明ＳＮＰ释放的ＮＯ过量积累可能是导致ｇ１２细胞遗传毒性的主要原因。Inductions of mutation and micronuclei(MN) by nitric oxide(NO),released chronically from the NO donor SNP,were investigated in mammalian cells.The results showed that the concentration of NO 2 - in medium rose according to time- and dose-exposed to SNP.The treatment of SNP(2-8 mM,without or with S9)induced a dose-response increase in the mutation frequncy at the gpt gene locus in g12 cells and a 13-fold(-S9) or 25-fold(+S9) increase above background levels in the highest tested dose.A statistically significant increase in the number of binucleated cell containing MN(MNBN) was also observed in treated groups.MNBN‰,MN‰ and proportion of multiple micronucleated cells increased in a dose-response manner within the range of dosage of SNP(0.5-4 mM,+S9 or 2-4 mM,-S9).Our results indicated that the excessive NO, released by SNP, might be a primary cause leading to genotoxicity in g12 cells.

关 键 词：硝普钠 遗传毒性 一氧化氮供体药 

分 类 号：R965.3[医药卫生—药理学]