Profound variation in dihydropyrimidine dehydrogenase activity in human blood cells: major implications for the detection of partly deficient patients

Dihydropyrimidine dehydrogenase (DPD) is responsible for the breakdown of t he widely used antineoplastic agent 5-fluorouracil (5FU), thereby limiting the efficacy of the therapy. To identify patients suffering from a complete or partial DPD deficiency. the activity of DPD is usually determined in pe ripheral blood mononuclear cells (PBM cells). In this study, we demonstrate d that the highest activity of DPD was found in monocytes followed by that or lymphocytes, granulocytes and platelets, whereas no significant activity of DPD could be detected in erythrocytes. The activity of DPD in PBM cells proved to be intermediate compared with the DPD activity observed in monoc ytes and lymphocytes. The mean percentage of monocytes in the PBM cells obt ained from cancer patients proved to be significantly higher than that obse rved in PBM cells obtained from healthy volunteers. Moreover, a profound po sitive correlation was observed between the DPD activity of PBM cells and t he percentage of monocytes, thus introducing a large inter- and intrapatien t variability in the activity of DPD and hindering the detection of patient s with a partial DPD deficiency.