DNA DAMAGE AND MUTATION IN HUMAN-CELLS EXPOSED TO NITRIC-OXIDE INVITRO
DNA DAMAGE AND MUTATION IN HUMAN-CELLS EXPOSED TO NITRIC-OXIDE INVITRO
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DOI：
10.1073/pnas.89.7.3030
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发表时间：
1992-04-01
影响因子：
11.1
通讯作者：
TANNENBAUM, SR
中科院分区：
文献类型：
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作者：
NGUYEN, T;BRUNSON, D;TANNENBAUM, SR
一氧化氮（NO.）是由几种细胞类型形成的生理信使。与O2反应形成氧化物，在pH值接近7时亚硝化胺。我们现在报告的实验中，NO。添加到完整的人类细胞和DNA、RNA、鸟嘌呤或腺嘌呤的有氧溶液中。TK6人淋巴母细胞样细胞在HPRT和TK基因位点上的突变比背景水平高15- 18倍。在所有情况下，分别由鸟嘌呤和腺嘌呤脱胺形成黄嘌呤和次黄嘌呤。否。诱导剂量反应性DNA链断裂。黄嘌呤的产量几乎等于次黄嘌呤的80倍。从核酸中提取黄嘌呤和次黄嘌呤的产率高于游离鸟嘌呤和腺嘌呤。这在黄嘌呤中最为明显；游离鸟嘌呤生成0.3 nmol/mg，小牛胸腺RNA生成550 nmol/mg。添加到TK6细胞中的一氧化氮使细胞DNA中的次黄嘌呤和黄嘌呤增加了40至50倍。我们相信这些结果，加上预期的胞嘧啶到尿嘧啶和5-甲基胞嘧啶到胸腺嘧啶的脱氨，解释了一氧化氮对细菌和哺乳动物细胞的诱变性。
Nitric oxide (NO.) is a physiological messenger formed by several cell types. Reaction with O2 forms oxides that nitrosate amines at pH values near 7. We now report experiments in which NO. was added to intact human cells and to aerobic solutions of DNA, RNA, guanine, or adenine. TK6 human lymphoblastoid cells were mutated 15- to 18-fold above background levels at both the HPRT and TK gene loci. Xanthine and hypoxanthine, from deamination of guanine and adenine, respectively, were formed in all cases. NO. induced dose-responsive DNA strand breakage. Yields of xanthine ranged from nearly equal to about 80-fold higher than those of hypoxanthine. Yields of xanthine and hypoxanthine from nucleic acids were higher than those from free guanine and adenine. This was most pronounced for xanthine; 0.3 nmol/mg was formed from free guanine vs. 550 nmol/mg from calf thymus RNA. Nitric oxide added to TK6 cells produced a 40- to 50-fold increase in hypoxanthine and xanthine in cellular DNA. We believe that these results, plus the expected deaminations of cytosine to uracil and 5-methylcytosine to thymine, account for the mutagenicity of nitric oxide toward bacteria and mammalian cells.