DNA damage and mutation in human cells exposed to nitric oxide in vitro
摘要:
Nitric oxide (NO·) is a physiological messenger formed by several cell types. Reaction with O2forms 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.
展开
关键词:
DOI:
10.1073/pnas.89.7.3030
被引量:
年份:
1992
















































通过文献互助平台发起求助,成功后即可免费获取论文全文。
相似文献
参考文献
引证文献
来源期刊
研究点推荐
引用走势
辅助模式
引用
文献可以批量引用啦~
欢迎点我试用!