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

Citation
M. Andou et al., Decreased fluorouracil cytotoxic effect on EB-virus transformed lymphocytes from hereditary orotic aciduria, INT J MOL M, 6(1), 2000, pp. 69-72
Citations number
12
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medical Research General Topics
Journal title
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
ISSN journal
1107-3756 → ACNP
Volume
6
Issue
1
Year of publication
2000
Pages
69 - 72
Database
ISI
SICI code
1107-3756(200007)6:1<69:DFCEOE>2.0.ZU;2-9
Abstract
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.