Enhanced antitumor activity of 5'-deoxy-5-fluorouridine against Lewis lung carcinoma in aged hybrid (C57BL/6 x DBA/2) F1 mice.
The antitumor activity of 5'-deoxy-5-fluorouridine (5'-DFUR) against Lewis lung carcinoma was examined by implanting the tumor subcutaneously into young (8-11 weeks) and old (24-41 weeks) hybrid (C57BL/6 x DBA/2)F1 (BDF1) male mice. Oral administration of 5'-DFUR induced a small (7 of 100) but significant (p less than 0.05) number of 70-d survivors in young mice. However, the antitumor activity was further enhanced in the old mice, and 15 of 46 (32.6%) and 11 of 62 (17.7%) mice survived for 70-d by treatment with 2000 and 1000 mg 5'-DFUR/kg/d, respectively, given on days 1, 5, and 9. The reason for the higher cure rate in old mice was partly analyzed. Toxicity of 5'-DFUR in young and old mice did not differ significantly, regardless of the presence (except 2000 mg/kg) or absence of Lewis lung carcinoma. No survivors were observed after treatment with 5'-DFUR when the tumors were implanted into the aged (15-38 weeks) syngeneic hosts, C57BL/6 mice. On the other hand, the survival time of BDF1 mice implanted with a constant number of the tumor cells increased significantly with the increase in host age and reached a maximum at the age of 24 weeks. These findings suggest that an optimal activation of 5'-DFUR (to 5-FU) was carried out in the old BDF1 mice bearing Lewis lung carcinoma and/or that a host-mediated antitumor mechanism of BDF1 mice, which is reinforced with aging, might participate in the enhancement of the antitumor activity of 5'-DFUR against this tumor.
D000367:Age Factors; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D005467:Floxuridine / Q000627:therapeutic use* / Q000633:toxicity; D006824:Hybridization, Genetic; D007928:Lethal Dose 50; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000401:mortality; D011355:Prodrugs; D014543:Uridine Phosphorylase / Q000032:analysis
D000970:Antineoplastic Agents; D011355:Prodrugs; D005467:Floxuridine; D014543:Uridine Phosphorylase; C025034:doxifluridine