Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.3.5.5 (CPS)
 1,262 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study was made of the in vivo effects of equitoxic doses of AT-125 and 5-FU combination, being administered either simultaneously (% ILS 152) or with a 6-h pretreatment with AT-125 (% ILS 184). To examine the biochemical basis for the scheduled synergism, measurements were made of the concentration of PRPP, the specific activities of CPS II, cytidine, thymidine, uridine, deoxyuridine kinases, and fluorinated nucleotide formation in P388 tumors and the small intestine. Two hours after in vivo simultaneous treatment of mice bearing tumors the concentration of PRPP increased 9- and 6-fold above baseline in the tumor and the small intestine, respectively. In the AT-125 pretreatment arm the concentration of PRPP increased 18- and 7-fold above baseline in the tumor and the small intestine, respectively. CPS II activity was reduced to 28%-18% of control in the tumors in the simultaneous and pretreatment groups, respectively, whereas it remained unchanged in the small intestine. Specific activities of cytidine kinase (5.5 +/- 1), thymidine kinase (4.0 +/- 1.6), uridine kinase (35.6 +/- 6.5), and deoxyuridine kinase (2.4 +/- 1.1) nmol/mg protein/h remained unchanged with treatment. In concert with the increased intratumor concentration of PRPP, fluorinated nucleotide formation was proportionally increased in the treatment arms. These results indicate the importance of drug scheduling of the above two agents in treating P388 leukemia.
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PMID:Biochemical mechanisms for the scheduled synergism of (alpha S, 5S)-2 amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid and 5-fluorouracil in P388 leukemia. 240 73

1. The incorporation of thymidine into DNA of regenerating rat liver was measured at various times after partial hepatectomy. A single intravenous injection of 30mumol of beryllium/kg given immediately after the operation inhibited DNA synthesis 12, 16, 20, 24 and 28h later. 2. The activity of several enzymes critical to DNA synthesis (thymidine kinase, thymidylate kinase, thymidylate synthetase, deoxycytidylate deaminase and DNA polymerase) increased in control rats 20-24h after partial hepatectomy severalfold over the activity found in resting livers. After beryllium treatment this rise in activity was much less and it seemed as if beryllium would partially block the induction of DNA-synthesizing enzymes after partial hepatectomy. 3. Enzymes whose activities do not rise during liver regeneration were not affected by beryllium (aspartate transcarbamoylase, carbamoyl phosphate synthetase, uridine kinase and glucose 6-phosphatase). 4. No evidence was found in vitro that beryllium would specifically inhibit thymidine kinase or DNA polymerase. 5. The time-effect relationship between beryllium administration and thymidine kinase activity in vivo was examined. Measured 24h after partial hepatectomy, thymidine kinase activity was only affected if beryllium was given within the first 9-12h after partial hepatectomy. Beryllium given later, even in greatly increased doses, failed to have any effect on thymidine kinase. The possibility is discussed that beryllium inhibits enzyme induction at the transcriptional level.
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PMID:Effects of beryllium on deoxyribonucleic acid-synthesizing enzymes in regenerating rat liver. 549 75