The effect of methotrexate pretreatment on 5-fluorouracil kinetics in sarcoma 180 in vivo.
Synergy of sequential MTX and 5-FU has been shown in several in vitro and in vivo systems. In the present study the influence of time interval between MTX and 5-FU and MTX dose on 5-FU accumulation in tumor cells has been examined in Sarcoma 180 in vivo. There was a clear relationship between MTX dose applied and amount of 5-FU detected in the acid-soluble fraction, the RNA fraction and the thymidylate synthase complex fraction. Also, the MTX-5-FU time interval affected clearly the amount of 5-FU detected in all three fractions, the optimum time interval being 8-12 hr. The results indicate that for sequential application of MTX and 5-FU selection of an adequate MTX dose and a sufficient time interval is crucial to achieve synergistic action.
D000818:Animals; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000378:metabolism*; D007700:Kinetics; D008727:Methotrexate / Q000008:administration & dosage*; D051379:Mice; D012334:RNA, Neoplasm / Q000378:metabolism; D012510:Sarcoma 180 / Q000201:enzymology / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000378:metabolism
D012334:RNA, Neoplasm; D013940:Thymidylate Synthase; D005472:Fluorouracil; D008727:Methotrexate