Oxidants generated by eosinophils during chronic inflammation may
lead to mutagenesis in adjacent epithelial cells. Eosinophil
peroxidase, a heme enzyme released by eosinophils, generates
hypobromous acid that damages tissue in inflammatory conditions. We
show that human eosinophils use eosinophil peroxidase to produce
5-bromodeoxycytidine. Flow cytometric, immunohistochemical, and mass
spectrometric analyses all demonstrated that 5-bromodeoxycytidine
generated by eosinophil peroxidase was taken up by cultured cells and
incorporated into genomic DNA as 5-bromodeoxyuridine. Although previous
studies have focused on oxidation of chromosomal DNA, our observations
suggest another mechanism for oxidative damage of DNA. In this
scenario, peroxidase-catalyzed halogenation of nucleotide precursors
yields products that subsequently can be incorporated into DNA. Because
the thymine analog 5-BrUra mispairs with guanine in DNA, generation of
brominated pyrimidines by eosinophils might constitute a mechanism for
cytotoxicity and mutagenesis at sites of inflammation.