Abstract：
:5,10-Dideazatetrahydrofolic acid (DDATHF) reduces de nova purine biosynthesis by inhibiting glycinamide ribonucleotide transformylase. ICI D1964 and CB3717 are folate-based inhibitors of thymidylate synthase (TS). Fluorodeoxyuridine (FdUrd) following metabolism to FdUMP also inhibits TS. In cultured L1210 cells DDATHF reduced the toxicity of ICI D1694, CB3717 and FdUrd in a concentration-dependent manner. This protection correlated with a prevention of the increase in intracellular dATP pools seen in cells exposed to the TS inhibitors alone. The possibility that DDATHF protection might be due to competition for cell entry is not likely since CB3717 and FdURD but not ICI D1694 enter the cell by independent transport processes. Exogenous hypoxanthine (HX) had no effect on the toxicity of TS inhibitors. However, HX increased the protective effect of DDATHF from ICI D1694 toxicity, had no effect on the CB3717-DDATHF interaction, and reduced the protective effect of DDATHF on FdUrd toxicity. HX prevented the fall in dATP levels caused by DDATHF addition to cells treated with TS inhibitors. HX had different effects on dTTP levels in cells treated with DDATHF and quinazoline TS inhibitors compared to FdUrd. Together these results support the hypothesis that imbalance in dTTP and dATP pools is an important determinant of cytotoxicity in antifolate-treated cells. In addition, these findings suggests that intracellular reduced folates interconvert to catalyse reactions in metabolically perturbed cells.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Chong LK,Tattersall MHdoi
10.1016/0006-2952(94)00458-xsubject
Has Abstractpub_date
1995-03-15 00:00:00pages
819-27issue
6eissn
0006-2952issn
1873-2968pii
000629529400458Xjournal_volume
49pub_type
杂志文章abstract：:The effects of cetaben and clofibric acid were compared on the activities of peroxisomal enzymes in the liver and kidney of male Wistar rats. Cetaben at 200 mg/kg body wt increased the activities of all of the enzymes in the liver that were studied two to eight times, whereas the changes induced by the same dose of cl...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90183-x
更新日期：1994-02-09 00:00:00
abstract：:Inhibition of glycogen synthase kinase (GSK)-3 and the consequent activation of the Wnt/β-catenin signaling pathway have been reported to increase bone volume. To develop a novel pharmacotherapy for injured bone, we investigated whether GSK-3 inhibitor was effective in promoting bone formation. In in vitro experiments...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2014.06.011
更新日期：2014-08-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)02442-5
更新日期：1996-07-26 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90170-2
更新日期：1993-02-24 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2007.02.014
更新日期：2007-08-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.114144
更新日期：2020-10-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2012.06.012
更新日期：2012-09-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)02104-3
更新日期：1995-12-22 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90459-x
更新日期：1987-11-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90245-g
更新日期：1990-11-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00250-1
更新日期：2000-05-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2016.02.015
更新日期：2016-05-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90207-3
更新日期：1987-09-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00535-9
更新日期：2001-01-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90500-2
更新日期：1994-11-29 00:00:00
abstract：:Guinea pig gallbladder muscle strips were used to investigate the contribution of different sources of diacylglicerol (DAG) in the cholecystokinin (CCK)-induced contraction. The involvement of arachidonic acid (AA) in this response was also investigated. Three distinct pathways for DAG production were investigated wit...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(02)01259-5
更新日期：2002-10-01 00:00:00
abstract：:The effect of ifosfamide and its metabolites on intracellular levels of glutathione in P388 cells in vitro has been studied. It is demonstrated that glutathione depletion occurs only in the presence of 4-hydroperoxyifosfamide and chloroacetaldehyde. In contrast isophosphoramide mustard had no effect on glutathione lev...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90419-x
更新日期：1989-06-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(98)00174-9
更新日期：1998-08-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90514-w
更新日期：1993-08-03 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90156-d
更新日期：1992-06-23 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.11.001
更新日期：2012-01-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2008.02.007
更新日期：2008-05-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.06.009
更新日期：2007-09-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90123-z
更新日期：1992-09-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00412-x
更新日期：2003-09-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.06.003
更新日期：2006-09-14 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90180-5
更新日期：1993-02-24 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90464-3
更新日期：1987-11-15 00:00:00
abstract：:A marked genetic variation in the capacity to perform xenobiotic metabolism was observed in microsomal fractions from the seven Drosophila strains studied. A 1,5 to 2-fold variation was found in the content of cytochrome P-450 and in the NADPH-cytochrome c reductase activity. The two insecticide-resistant strains Hiko...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90364-2
更新日期：1984-01-01 00:00:00
abstract：:Protein phosphatases are responsible for keeping the signaling output of stimulus-activated protein kinases in check; but protein phosphatases are also themselves targets and conveyors of biological signals. Among the major serine/threonine phosphatases, protein phosphatase 2A (PP2A) appears to play a privileged role ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0006-2952(98)00245-7
更新日期：1999-02-15 00:00:00
