Incorporation of metabolites of 2'-fluoro-5-iodo-1-beta-D-arabinofuranosylcytosine into deoxyribonucleic acid of neoplastic and normal mammalian tissues.

The radioactivity of 14C-labeled 2'-fluoro-5-iodo-1-beta-D-arabinofuranosylcytosine ([2-14C]-FIAC), a new and potent antiherpetic agent, was shown previously to be incorporated into the DNA fractions of mammalian and neoplastic tissues. The present work was undertaken to learn the nature of the incorporated moieties. Enzyme degradation of highly purified DNA from the small intestine of mice treated with [2-14C]FIAC and analysis of the resulting nucleosides failed to reveal the presence of unchanged FIAC. Rather, three metabolites were found, namely, the 2'-fluoro-1-beta-D-arabinofuranosyl nucleosides of cytosine (FAC), thymine (FMAU) and 5-iodouracil (FIAU). Labeled metabolites of FIAC were also found in the DNA isolated from P815 leukemic cells in mice given [2-14C]FIAC. It is of interest to note that FMAU, FIAU and FAC are, like FIAC, potent antiherpetic agents.