Metabolic Enzymes of 5-Fluorouracil and Messenger RNA Levels May Concern with the Sensitivity to 5-Fluorouracil.

Abstract

We investigated the correlation between tumor sensitivity to 5-fluorouracil (5-FU) and enzymatic activities of thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) using human tumor xenografts and human gastric cancer specimens. DPD levels significantly correlated with 5-FU sensitivity, such that high DPD activity and high DPD mRNA levels resulted in low sensitivity to 5-FU. In contrast, no correlation was observed between TS activity or TS mRNA levels and 5-FU sensitivity. The tumor DPD mRNA level may be a useful indicator in predicting tumor sensitivity to 5-FU.