Sequential methotrexate/5-FU: FdUMP formation and TS inhibition in a transplantable rodent colon adenocarcinoma.

Parameters for inhibition of thymidylate synthetase were studied after sequential methotrexate/5-fluorouracil (5-FU) administration in a dimethylhydrazine (DMH)-induced transplantable rat colon carcinoma. Tumor-bearing rats were treated with methotrexate (MTX) 40 mg/kg IP Bolus 5-FU, 100 mg/kg IP, was injected after 24 h. Micromethods for assay of 5-fluoro-2′-deoxyuridylate (FdUMP) and thymidylate synthetase (TS) were used to study the in vivo intracellular pharmacokinetics of 5-FU.