Hypochlorite-modified adenine nucleotides: structure, spin-trapping, and formation by activated guinea pig polymorphonuclear leukocytes.

Adenosine and its nucleotides react with hypochlorite to form unstable products that have been identified as the N6 chloramine derivatives. These chloramines spontaneously oligomerize, form stable adducts with proteins and nucleic acids, and are converted with loss of chlorine to the original nucleoside or nucleotide by reducing agents. The chloramines are associated with a free radical, and the spin-trapping of adenosine chloramine with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) yielded a mixture of unstable nitroxyl adducts that corresponded to nitrogen-centered radicals from the parent nucleoside. When activated guinea pig polymorphonuclear leukocytes were stimulated with phorbol myristate acetate to produce hypochlorite, they actively incorporated [14C]adenosine into acid-insoluble products by a process that was dependent on oxygen and inhibited by azide and thiols. These findings suggest that adenine nucleotide chloramines are generated by activated phagocytic cells and form ligands with proteins and nucleic acids as observed in model systems. The results imply that nucleotide chloramines are among the cytotoxic and possibly mutagenic factors that are associated with the inflammatory process.