Dihydropyrimidine dehydrogenase activity in normal, inflammatory and tumour tissues of colon and liver in humans

Background/Purpose: Dihydropyridmidine dehydrogenase (DPD) is the initial a nd rate-limiting enzyme in the catabolism of 5-fluorouracil (5FU). Although this catabolism is likely to occur in the liver in humans, there may be a local inactivation in tumours, modifying the efficacy of 5FU. The aim of th is study was to examine the DPD activity in normal, inflammatory and malign ant tissues from both the colon and the liver to assess the modifications o f DPD activity in the process of tumourigenesis. Methods: DPD activity was evaluated in 107 patients, corresponding to 194 samples (70 colorectal tumo ur and normal colon, nine metastases secondary to a colon cancer, ten infla mmatory colon, 20 samples of normal liver, seven from primary liver cancer, and eight from inflammatory liver). DPD activity was determined using an e nzymatic reaction followed by analysis of 5FU and its catabolite dihydro-5F U by highperformance liquid chromatograph. Results were expressed as pmol o f 5FU catabolized/min . mg protein. Results: DPD was highly variable in tum our and normal tissues, both fi om colon and liver. In colon, the correlati on between DPD activity in tumour and normal mucosa was weak, even if it wa s statistically significant due to the higher number of samples. In inflamm atory colon tissue (ulcerative colitis or Crohn's disease), DPD activity wa s significantly higher than in normal tissue (P = 0.006). In liver metastas es from colon cancer, DPD activity was not significantly different from tha t observed in primary colon tumour (P = 0.32). In liver, DPD activity was s ignificantly lower in primary liver tumour than in uninvolved liver specime ns (P = 0.001). In inflammatory liver tissue (hepatitis), DPD activity rang ed between normal and tumour tissues, and did not differ significantly eith er from normal tissue or primary liver cancer. Conclusions: DPD activity wa s modified in colon and in liver during a pathological process and the dysr egulation of DPD increased from a benign to a malignant tissue.