Gf. Fleming et al., PERIPHERAL-BLOOD MONONUCLEAR CELL DIHYDROPYRIMIDINE DEHYDROGENASE-ACTIVITY IN VOLUNTEERS WITH AND WITHOUT DIABETES-MELLITUS, Cancer chemotherapy and pharmacology, 37(6), 1996, pp. 569-573
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.