Relationship between intratumoral dihydropyrimidine dehydrogenase activity and gene expression in human colorectal cancer

Abstract

Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme for 5-fluorouracil catabolism. In this study, both the enzymatic activity and mRNA level of DPD were estimated in the tumor tissue and adjacent normal mucosa of 51 patients with colorectal cancer. Although no significant difference in enzymatic activity was observed between tumor tissue and normal mucosa (70.4 and 70.7 pmol/min/mg protein, respectively), the mRNA level in normal mucosa was significantly higher than that in tumor tissue (1.37 and 0.39, respectively; P<0.01). A linear relationship was noted between DPD activity and the DPD mRNA level in cancerous tissue (r(s) = 0.714, P<0.001). Thus, the DPD mRNA level as determined by reverse transcription-PCR can be used to indicate the DPD activity of colorectal cancers.