The study investigates the effects of nitric oxide (NO) on DNA damage and mutation in human cells. NO, a physiological messenger, reacts with oxygen to form nitrosating agents that can nitrosate amines at pH values near 7. The researchers exposed TK6 human lymphoblastoid cells to NO and found that it induced a 15- to 18-fold increase in the mutant fraction at both the HPRT and TK gene loci. NO also caused dose-responsive DNA strand breaks and the formation of xanthine and hypoxanthine from guanine and adenine, respectively. The yields of xanthine were significantly higher than those of hypoxanthine, and the yields from nucleic acids were higher than from free bases. The study suggests that the mutagenicity of NO may be due to the deamination of cytosine to uracil and 5-methylcytosine to thymine, in addition to the observed DNA damage. The results indicate that cytotoxicity and mutagenicity associated with the inflammatory process may result from nitrogen oxide radicals, in addition to the well-known reactions of oxygen radicals.The study investigates the effects of nitric oxide (NO) on DNA damage and mutation in human cells. NO, a physiological messenger, reacts with oxygen to form nitrosating agents that can nitrosate amines at pH values near 7. The researchers exposed TK6 human lymphoblastoid cells to NO and found that it induced a 15- to 18-fold increase in the mutant fraction at both the HPRT and TK gene loci. NO also caused dose-responsive DNA strand breaks and the formation of xanthine and hypoxanthine from guanine and adenine, respectively. The yields of xanthine were significantly higher than those of hypoxanthine, and the yields from nucleic acids were higher than from free bases. The study suggests that the mutagenicity of NO may be due to the deamination of cytosine to uracil and 5-methylcytosine to thymine, in addition to the observed DNA damage. The results indicate that cytotoxicity and mutagenicity associated with the inflammatory process may result from nitrogen oxide radicals, in addition to the well-known reactions of oxygen radicals.