The distribution of
cyclocytidine and
cytosine arabinoside has been studied in normal BDF mice and in mice bearing 6-day solid L1210
lymphocytic leukemia by whole-body radioautography, bioassay, and radiochemical techniques. Radioactivity was widely distributed throughout the tissues between 15 minutes and 12 hours after a single intravenous dose of either cyclocytidine-2-14C or
cytosine arabinoside-2-14C. Whole-body radioautograms demonstrated that for most tissues,
cytosine arabinoside-derived 14C was uniformly excreted by 48 hours;
cyclocytidine-derived 14C, however, was localized in certain tissues as early as 15 minutes after
drug administration and was retained in these sites for 48 hours. Depot loci of 14C included salivary and adrenal glands, fat, cardiac muscle, gastrointestinal tract, and L1210
tumor. The distribution and persistence of
cyclocytidine-derived radioactivity is consistent with other reports of toxicity induced by the
drug in these tissues. Radiochromatography and bioassay data from BDF mice dosed intraperitoneally with
cyclocytidine demonstrated that 65%-95% of the 14C-radioactivity in a number of tissues was the parent compound itself. Thus,
cyclocytidine contributed in large measur to the generation of the radioautograms. This study demonstrates that the retention of
cyclocytidine in body tissues may serve to effect the sustained release of the deaminase-resistant chemotherapeutic
drug from these depot sites and thus prolong cytotoxic levels of
drug in
tumor tissue.