POPULATION CHARACTERISTICS OF HEPATIC DIHYDROPYRIMIDINE DEHYDROGENASE-ACTIVITY, A KEY METABOLIC ENZYME IN 5-FLUOROURACIL CHEMOTHERAPY

Dihydropyrimidine dehydrogenase is the initial rate-limiting enzyme in catabolism of 5-fluorouracil, one of the most widely used cancer chem otherapeutic agents. Previous studies have shown the clinical importan ce of determination of dihydropyrimidine dehydrogenase in patients wit h cancer, particularly in those with deficiency of this enzyme who exp erience severe 5-fluorouracil-associated toxicity (including death) af ter 5-fluorouracil treatment. In the present study, dihydropyrimidine dehydrogenase activity was determined in 138 donor liver samples, A no rmal distribution of human liver dihydropyrimidine dehydrogenase activ ity was shown. The mean enzyme activity was compared across different groups by age, gender, and race, with no significant differences obser ved except that the mean enzyme activity in women was slightly higher than that observed in men. With use of a polyclonal antibody generated against human liver dihydropyrimidine dehydrogenase, Western blot ana lysis showed that dihydropyrimidine dehydrogenase protein in the liver cytosol correlated with the activity of this enzyme.