DNA DEAMINATING ABILITY AND GENOTOXICITY OF NITRIC-OXIDE AND ITS PROGENITORS
DNA DEAMINATING ABILITY AND GENOTOXICITY OF NITRIC-OXIDE AND ITS PROGENITORS
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DOI：
10.1126/science.1948068
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发表时间：
1991-11-15
期刊：
影响因子：
56.9
通讯作者：
KEEFER, LK
中科院分区：
文献类型：
--
作者：
WINK, DA;KASPRZAK, KS;KEEFER, LK
一氧化氮（NO）是一种多方面的生物调节剂和环境污染物，也可以引起基因组改变。在体外，NO脱胺脱氧核苷、脱氧核苷酸和生理ph下的完整DNA。通过用三种NO释放化合物（包括硝酸甘油）处理鼠伤寒沙门氏菌TA1535，测试了体内类似的DNA损伤也可能发生。都被证明具有诱变性。观察到的DNA序列变化是hisG46 （CCC）靶密码子中的> -> T转移，与胞嘧啶脱氨机制一致。由于暴露于内源性和外源性一氧化氮是广泛的，这一机制可能有助于脱氨相关遗传疾病和癌症的发生。
Nitric oxide (NO), a multifaceted bioregulatory agent and an environmental pollutant, can also cause genomic alterations. In vitro, NO deaminated deoxynucleosides, deoxynucleotides, and intact DNA at physiological pH. That similar DNA damage can also occur in vivo was tested by treating Salmonella typhimurium strain TA1535 with three NO-releasing compounds, including nitroglycerin. All proved mutagenic. Observed DNA sequence changes were > 99% C --> T transitions in the hisG46 (CCC) target codon, consistent with a cytosine-deamination mechanism. Because exposure to endogenously and exogenously produced NO is extensive, this mechanism may contribute to the incidence of deamination-related genetic disease and cancer.