[Comparison between leucovorin and cisplatin as a modulator of 5-fluorouracil].
Currently, biochemical modulation for 5-fluorouracil (5-FU) by leucovorin (LV) and cisplatin (CDDP) seems one of the most successful chemotherapy for gastro-intestinal tract cancers. The mechanism of the modulation is thought to increase intracellular 5, 10-methylenetetrahydrofolate (CH2-H4 folate) levels. The purpose of this study is to examine the effect of LV and CDDP as a modulator of 5-FU. Either 10, 200, 400 mg/kg of LV or 2, 4, 6 mg/kg of CDDP were administered intravenously to mice bearing Sarcoma-180. Two hrs. later, CH2-FH4 folate levels were measured in tumor, muscle and intestine by thymidylate synthase (TS) binding assay. As the results, after administration of 200, 400 mg/kg of LV or 4, 6 mg/kg of CDDP, CH2-H4 folate level was elevated. This elevation was dose-dependent in LV. In contrast, no more elevation was observed after 6 mg/kg of CDDP injection. There was much smaller increase of CH2-H4 folate level was observed in the muscle and intestine. We conclude that the elevation of CH2-H4 folate levels depends on the organ and this leads to the tumor specificity in these chemotherapy.
Iba
T
T
Dept. of Surgery, Juntendo University School of Medicine, Urayasu Hospital.
Yagi
Y
Y
Kidokoro
A
A
Fukunaga
T
T
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology*; D002955:Leucovorin / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D012510:Sarcoma 180 / Q000737:chemistry / Q000473:pathology*; D013763:Tetrahydrofolates / Q000378:metabolism; D013940:Thymidylate Synthase
D013763:Tetrahydrofolates; C013123:5,10-methylenetetrahydrofolic acid; D013940:Thymidylate Synthase; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil