Nitric oxide (NO) induces DNA damage and mutations in human cells. When added to TK6 human lymphoblastoid cells, NO caused a 15- to 18-fold increase in mutations at the HPRT and TK gene loci. NO also caused DNA strand breaks, with xanthine yields being 80-fold higher than hypoxanthine. Nitric oxide deaminates purine bases, leading to mutations and DNA damage. These effects are likely due to the formation of N2O3, a nitrosating agent, which reacts with amino groups in DNA. NO can also cause depurination and strand breaks, contributing to cytotoxicity and mutagenicity. The study shows that NO-induced DNA damage is more severe than that from other mutagens, and that NO can cause both transitions and transversions in DNA bases. The results suggest that NO-induced mutagenicity is due to deamination of cytosine to uracil and 5-methylcytosine to thymine. The study also highlights the role of NO in inflammatory processes and its potential to cause mutations in mammalian cells. The findings have implications for understanding the role of NO in cancer and other diseases.Nitric oxide (NO) induces DNA damage and mutations in human cells. When added to TK6 human lymphoblastoid cells, NO caused a 15- to 18-fold increase in mutations at the HPRT and TK gene loci. NO also caused DNA strand breaks, with xanthine yields being 80-fold higher than hypoxanthine. Nitric oxide deaminates purine bases, leading to mutations and DNA damage. These effects are likely due to the formation of N2O3, a nitrosating agent, which reacts with amino groups in DNA. NO can also cause depurination and strand breaks, contributing to cytotoxicity and mutagenicity. The study shows that NO-induced DNA damage is more severe than that from other mutagens, and that NO can cause both transitions and transversions in DNA bases. The results suggest that NO-induced mutagenicity is due to deamination of cytosine to uracil and 5-methylcytosine to thymine. The study also highlights the role of NO in inflammatory processes and its potential to cause mutations in mammalian cells. The findings have implications for understanding the role of NO in cancer and other diseases.