Variability of thymidylate synthase activity in whole blood cultures treated with FUdR.

Autor: Sklower SL, Jenkins EC, Anderson ML, Chan CB, Brown WT
Jazyk: angličtina
Zdroj: American journal of medical genetics [Am J Med Genet] 1986 Jan-Feb; Vol. 23 (1-2), pp. 483-90.
DOI: 10.1002/ajmg.1320230140
Abstrakt: Induction of some fragile sites including fragile X [fra(X)] depends on the depletion of thymidine monophosphate (TMP) from the culture medium. This can be accomplished by use of inhibitors such as 5-fluorodeoxyuridine (FUdR) and by culturing cells in medium deficient in folate and TMP. FUdR inhibits the activity of thymidylate synthase (TS), thereby depleting cells of TMP. To determine the degree of FUdR inhibition of TS under routine cytogenetic culture conditions, we modified the tritiated dUMP TS method for use in short-term whole blood cultures stimulated with phytohemagglutinin. TS inhibition was highly variable across whole blood cultures from 30 individuals exposed to FUdR during the last 24 hours of a 4 day culture. If an additional dose of FUdR was added 12 hours before harvest, TS inhibition usually increased. These findings have a potential impact on the use of FUdR for the diagnosis of the fra(X) syndrome.
Databáze: MEDLINE