Inter- and intraindividual variation in dihydropyrimidine dehydrogenase activity in peripheral blood mononuclear cells

Cancer Chemotherapy and Pharmacology
J L GremC J Allegra

Abstract

The activity of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme in fluorouracil catabolism, has been reported to vary according to time of day. We wished to determine whether peak and trough DPD activities occurred at uniform times in six subjects, whether individual patterns fit a discernible profile, and whether such patterns were consistent and reproducible over time. Mononuclear cells were isolated from peripheral blood at 3-h intervals over a 24-h period on three different dates over a 6-month period. DPD activity was determined by incubating cellular lysates with [3H]FUra and measuring [3H]dihydrofluorouracil formation over time. When the data were averaged by study date for each subject, the median value for the average DPD activity (11.0 pmol/min per 10(6) cells) was significantly different from both the median peak (21.1 pmol/min per 10(6) cells, P = 0.004) and median trough activities (4.0 pmol/min per 10(6) cells, P = 0.002). Within the six subjects, the average DPD activity for the three study dates differed by a median of 2.4-fold (range 1.2- to 4.8-fold). The time at which peak and trough DPD activities occurred varied between subjects: 8 of the 17 peaks (47%) occurred between 10:00 p.m. and 6:00 a...Continue Reading

Citations

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