ACCUMULATION OF 5-ETHYL-2'-DEOXYURIDINE AND ITS 5,6-DIHYDRO PRODRUGS IN MURINE LUNG AND ITS POTENTIAL CLINICAL-APPLICATION

The accumulation of 5-ethyl-2'-deoxyuridine (EDU), bromo-5-ethyl-6-met oxy-5,6-dihydro-2'-deoxyuridine [(5S,6S)-BMEDU], romo-5-ethyl-6-methox y-5,6-dihydro-2'-deoxyuridine [(5R,6R)-BMEDU], bromo-5-ethyl-6-ethoxy- 5,6-dihydro-2'-deoxyuridine (BEEDU), (+)-trans-(5R,6R)- -6-ethoxy-5,6- dihydro-5'-O-valeryl-2'-deoxyuridine (VBEEDU) and oxy-5,6-dihydro-3'-5 '-di-O-valeryl-2'-deoxyuridine (DVBEEDU) in lung and other tissues was investigated in male Balb-C mice following intravenous injection of t he corresponding 4-C-14-labelled compounds. EDU showed a rapid distrib ution into liver and lung immediately after injection, and the overall levels of radioactivity in blood, liver and lung were similar. The di stribution of radioactivity in lung after injection of [4-C-14](5S,6S) -BMEDU and [4-C-14](5R,6R)-BMEDU were substantially different from one another and also from that of [4-C-14]EDU. The radioactivity level pr esent in lung samples after injection of both [4-C-14](5S,6R)-BMEDU an d [4-C-14](5R,6R)-BMEDU was substantially higher than that in blood sa mples. Radioactivity levels present in lung samples taken at 18 min af ter injection of [4-C-14]BEEDU were significantly higher (P < 0.05) th an those for liver and blood samples. Although the radioactivity prese nt in lung samples after injection of [4-C-14]VBEEDU was significantly higher (P < 0.05) than those of liver and blood samples, [4-C-14]VBEE DU did not provide a higher radioactivity level in lung samples than d id [4-C-14]BEEDU. The level of radioactivity in lung samples following injection of [4-C-14]DVBEEDU was also higher than that of blood sampl es. EDU undergoes glycosidic bond cleavage to form EU in lung followin g intravenous injection into Balb-C mice. The concentrations of EDU an d 5-ethyluracil (EU) following intravenous injection of EDU, and its p rodrugs BEEDU and VBEEDU, were quantitated in lung and blood samples. In contrast to lung samples, EU was not detected in blood samples at 1 20 min post injection of EDU. The concentrations of both EDU and EU in lung tissues after injection of BEEDU and VBEEDU were substantially h igher than those in blood samples.