ENHANCED ANTITUMOR ACTIVITY OF 5'-DEOXY-5-FLUOROURIDINE AGAINST LEWIS LUNG CARCINOMA IN AGED HYBRID (C57BL/6×DBA/2) F_1 MICE

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概要

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• 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×DBA/2) F_1 (BDF_1) male mice. Oral administration of 5'-DFUR induced a small (7 of 100) but significant (p<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 BDF_1 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 BDF_1 mice bearing Lewis lung carcinoma and/or that a host-mediated antitumor mechanism of BDF_1 mice, which is reinforced with aging, might participate in the enhancement of the antitumor activity of 5'-DFUR against this tumor.

• 公益社団法人日本薬学会の論文

著者

• Ogawa Makoto

  Division Of Clinical Chemotherapy Cancer Chemotherapy Center Japanese Foundation For Cancer Research

• Fujimoto Shuichi

  Division Of Chemotherapy Chiba Cancer Center Research Institute

• Fujimoto Shuichi

  Division Of Clinical Chemotherapy Cancer Chemotherapy Center Japanese Foundation For Cancer Research

• WANG YI

  Division of Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Resear

• Wang Yi

  Division Of Clinical Chemotherapy Cancer Chemotherapy Center Japanese Foundation For Cancer Research

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• ENHANCED ANTITUMOR ACTIVITY OF 5'-DEOXY-5-FLUOROURIDINE AGAINST LEWIS LUNG CARCINOMA IN AGED HYBRID (C57BL/6×DBA/2) F_1 MICE

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