PERIPHERAL-BLOOD MONONUCLEAR CELL DIHYDROPYRIMIDINE DEHYDROGENASE-ACTIVITY IN VOLUNTEERS WITH AND WITHOUT DIABETES-MELLITUS

It has been reported that cancer patients with diabetes mellitus recei ving a continuous infusion of 5-fluorauracil (5-FU) have more toxicity and higher plasma 5-FU levels than patients without diabetes mellitus . Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiti ng enzyme in the catabolism of 5-FU. DPD activity in peripheral blood mononuclear cells has been reported to correlate inversely with 5-FU p lasma levels in patients. We therefore undertook a study to compare th e activity of DPD in peripheral blood mononuclear cells of human subje cts with and without diabetes mellitus. The study groups comprised 43 volunteers with and 39 without diabetes mellitus, and peripheral blood mononuclear cell DPD activity was assayed on samples obtained between 8 a.m. and 11 a.m. DPD activity was not decreased in diabetic subject s. There was no relationship between DPD activity and gender, body mas s index, or race. There was a modest correlation between DPD activity and age (r = 0.19, P = 0.08). We conclude that increases in 5-FU-relat ed toxicities in diabetics must be related to factors other than perip heral blood mononuclear cell DPD activity.