GLUTATHIONE DEPLETION-INDUCED THYMIDYLATE INSUFFICIENCY FOR DNA-REPAIR SYNTHESIS

Citation
K. Lertratanangkoon et al., GLUTATHIONE DEPLETION-INDUCED THYMIDYLATE INSUFFICIENCY FOR DNA-REPAIR SYNTHESIS, Biochemical and biophysical research communications, 234(2), 1997, pp. 470-475
Citations number
29
Categorie Soggetti
Biology,Biophysics
ISSN journal
0006291X
Volume
234
Issue
2
Year of publication
1997
Pages
470 - 475
Database
ISI
SICI code
0006-291X(1997)234:2<470:GDTIFD>2.0.ZU;2-M
Abstract
Dietary methionine (Met) deficiency is known to divert folate away fro m de novo biosyntheses of purines and the pyrimidine, thymidylate, to the resynthesis of Met resulting in deoxynucleoside triphosphate imbal ance. We have recently shown that Met can easily be depleted and methy lation can be impaired by exposure to a model glutathione (GSH)-deplet ing agent, bromobenzene (BE). GSH depletion-induced Met depletion, the refore, could cause thymidylate insufficiency for DNA repair synthesis . The administration of thymidine (Thy) should repair this impairment. When this hypothesis was examined in the present study, several inter esting results were found. The administration of Thy labeled with [2-C -14]Thy to BB-treated Syrian hamsters at either 1, 5, 7 or 9 h after B B resulted in an attenuation of liver toxicity. Intrahepatic hemorrhag e, which is a typical characteristic of BE toxicity in the Syrian hams ter, was decreased in the BE + Thy groups. The attenuation of liver to xicity was accompanied by a progressive increase of Thy incorporation into liver genomic DNA at 24 h after BE. With respect to the time poin ts chosen for Thy administration, Thy incorporation found in the BE Thy groups were 2-, 2-, 3- and 4-fold of the controls that received on ly Thy. The results provide evidence that BE causes a progressive incr ease of thymidylate insufficiency in liver cells. Thymidylate insuffic iency is due to Met depletion, a depletion that occurs as a result of GSH depletion. (C) 1997 Academic Press.