Decreased fluorouracil cytotoxic effect on EB-virus transformed lymphocytes from hereditary orotic aciduria

5-Fluorouracil (5-FU), used widely for malignancies, phosphorylate mostly b y uracil phosphoribosyl transferase (UPRT). Patients with hereditary orotic aciduria lack the orotate phosphoribosyl transferase (OPRT) activity. In t he cancer cells, the OPRT activity is paralleled with the UPRT activity. Th is study shows that the UPRT activity of the hereditary orotic aciduria hom ozygote decreased about 40% of normal controls. Moreover, we investigated t he 5-FU cytotoxic effects on hereditary orotic aciduria tone homozygote, 4 heterozygotes and 7 normal controls), using EB-virus transformed lymphocyte s (EB-LC). 5-FU was addded to the culture medium at concentrations ranging from 0 to 10.0 mu mol/l. The 5-FU cytotoxic effects on the homozygote were milder than those on controls at each 5-FU concentration. The 5-FU cytotoxi c effects in the heterozygotes were at intermediate levels between the homo zygote and controls. We speculate that 5-FU cytotoxic effects, both anti-tu mor effects and adverse reactions, would be weak when a patient with heredi tary orotic aciduria was treated with 5-FU.