Abstract
Dietary methionine (Met) deficiency is known to divert folate away from de novo biosyntheses of purines and the pyrimidine, thymidylate, to the resynthesis of Met resulting in deoxynucleoside triphosphate imbalance. We have recently shown that Met can easily be depleted and methylation can be impaired by exposure to a model glutathione (GSH)-depleting agent, bromobenzene (BB). GSH depletion-induced Met depletion, therefore, 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 interesting results were found. The administration of Thy labeled with [2-14C]Thy to BB-treated Syrian hamsters at either 1, 5, 7 or 9 h after BB resulted in an attenuation of liver toxicity. Intrahepatic hemorrhage, which is a typical characteristic of BB toxicity in the Syrian hamster, was decreased in the BB + Thy groups. The attenuation of liver toxicity was accompanied by a progressive increase of Thy incorporation into liver genomic DNA at 24 h after BB. With respect to the time points chosen for Thy administration, Thy incorporation found in the BB + Thy groups were 2-, 2-, 3- and 4-fold of the controls that received only Thy. The results provide evidence that BIB causes a progressive increase of thymidylate insufficiency in liver cells. Thymidylate insufficiency is due to Met depletion, a depletion that occurs as a result of GSH depletion.
| Original language | English |
|---|---|
| Pages (from-to) | 470-475 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 234 |
| Issue number | 2 |
| DOIs | |
| State | Published - May 19 1997 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
Glutathione depletion-induced thymidylate insufficiency for DNA repair synthesis. / Lertratanangkoon, Khingkan; Savaraj, Niramol; Scimeca, Joseph M.; Thomas, Mary L.
In: Biochemical and Biophysical Research Communications, Vol. 234, No. 2, 19.05.1997, p. 470-475.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glutathione depletion-induced thymidylate insufficiency for DNA repair synthesis
AU - Lertratanangkoon, Khingkan
AU - Savaraj, Niramol
AU - Scimeca, Joseph M.
AU - Thomas, Mary L.
PY - 1997/5/19
Y1 - 1997/5/19
N2 - Dietary methionine (Met) deficiency is known to divert folate away from de novo biosyntheses of purines and the pyrimidine, thymidylate, to the resynthesis of Met resulting in deoxynucleoside triphosphate imbalance. We have recently shown that Met can easily be depleted and methylation can be impaired by exposure to a model glutathione (GSH)-depleting agent, bromobenzene (BB). GSH depletion-induced Met depletion, therefore, 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 interesting results were found. The administration of Thy labeled with [2-14C]Thy to BB-treated Syrian hamsters at either 1, 5, 7 or 9 h after BB resulted in an attenuation of liver toxicity. Intrahepatic hemorrhage, which is a typical characteristic of BB toxicity in the Syrian hamster, was decreased in the BB + Thy groups. The attenuation of liver toxicity was accompanied by a progressive increase of Thy incorporation into liver genomic DNA at 24 h after BB. With respect to the time points chosen for Thy administration, Thy incorporation found in the BB + Thy groups were 2-, 2-, 3- and 4-fold of the controls that received only Thy. The results provide evidence that BIB causes a progressive increase of thymidylate insufficiency in liver cells. Thymidylate insufficiency is due to Met depletion, a depletion that occurs as a result of GSH depletion.
AB - Dietary methionine (Met) deficiency is known to divert folate away from de novo biosyntheses of purines and the pyrimidine, thymidylate, to the resynthesis of Met resulting in deoxynucleoside triphosphate imbalance. We have recently shown that Met can easily be depleted and methylation can be impaired by exposure to a model glutathione (GSH)-depleting agent, bromobenzene (BB). GSH depletion-induced Met depletion, therefore, 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 interesting results were found. The administration of Thy labeled with [2-14C]Thy to BB-treated Syrian hamsters at either 1, 5, 7 or 9 h after BB resulted in an attenuation of liver toxicity. Intrahepatic hemorrhage, which is a typical characteristic of BB toxicity in the Syrian hamster, was decreased in the BB + Thy groups. The attenuation of liver toxicity was accompanied by a progressive increase of Thy incorporation into liver genomic DNA at 24 h after BB. With respect to the time points chosen for Thy administration, Thy incorporation found in the BB + Thy groups were 2-, 2-, 3- and 4-fold of the controls that received only Thy. The results provide evidence that BIB causes a progressive increase of thymidylate insufficiency in liver cells. Thymidylate insufficiency is due to Met depletion, a depletion that occurs as a result of GSH depletion.
UR - http://www.scopus.com/inward/record.url?scp=17144435821&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=17144435821&partnerID=8YFLogxK
U2 - 10.1006/bbrc.1997.6623
DO - 10.1006/bbrc.1997.6623
M3 - Article
C2 - 9177295
AN - SCOPUS:17144435821
VL - 234
SP - 470
EP - 475
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -