DIHYDROPYRIMIDINE DEHYDROGENASE-ACTIVITY IN HEPATOCELLULAR-CARCINOMA - IMPLICATION IN 5-FLUOROURACIL-BASED CHEMOTHERAPY

Dihydropyrimidine dehydrogenase (DPD) is the initial, rate-limiting en zyme in the catabolism of 5-fluorouracil, one of the most widely used cancer chemotherapeutic agents, Previous studies have demonstrated the clinical importance of determination of DPD in cancer patients, sugge sting that the efficacy and toxicity of 5-fluorouracil may directly re late to the DPD activity in both tumor and host tissues, In the presen t study, DPD activity was determined in 50 pairs of tumor and uninvolv ed liver specimens in Chinese cancer patients with hepatocellular carc inoma, Mean enzyme activity in uninvolved liver tissues (0.45 +/- 0.02 nmol/min/mg protein) was significantly higher than that in tumor spec imens (0.34 +/- 0.03 nmol/min/mg protein), Statistical analysis reveal ed no significant differences in DPD activity of tumor and uninvolved liver specimens among different age and gender groups, Compared to pre viously reported tumor studies, hepatomas were: found to have relative ly high DPD activity, Since high levels of DPD would be expected to me tabolize 5-fluorouracil, these findings may provide an explanation for the relative 5-fluorouracil resistance of hepatoma and may have impli cations for designing a new therapeutic strategy such as modulation of 5-fluorouracil chemotherapy by DPD inhibitors.