Thymidylate synthetase activity in the Novikoff hepatoma.

Abstract

The mechanism by which injected methotrexate increases thymidylate synthetase activity in the Novikoff hepatoma has been studied. Folic acid injection causes a similar increase in enzyme activity in hepatoma after 16 hr but the action of folic acid and methotrexate is not additive. The increase in activity of thymidine 5'-phosphate synthetase in the hepatoma caused by methotrexate is not affected by actinomycin D, but is inhibited 50% by puromycin and 100% by cycloheximide. High-speed supernatent fraction prepared from hepatoma of animals treated with methotrexate has, initially, one-half the specific thymidine 5'-phosphate synthetase activity of untreated controls. Upon addition of increasing amounts of tetrahydrofolate, the specific enzyme activity in the supernatant fraction from the methotrexate-treated animals rises to double that of the controls. Puromycin added to homogenates of Novikoff hepatoma consistently increases enzyme activity by approximately 20%. One hypothesis consistent with these results and results reported by others is presented.

• Authors: J J Roth, J S Roth
• Journal: Cancer research (Cancer Res) Vol. 36 Issue 12 Pg. 4500-3 (Dec 1976) ISSN: 0008-5472 [Print] United States
• PMID: 187325 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Tetrahydrofolates
• Dactinomycin
• Puromycin
• Folic Acid
• Cycloheximide
• Methyltransferases
• Thymidylate Synthase
• Methotrexate

Topics

• Animals
• Carcinoma, Hepatocellular (enzymology)
• Cycloheximide (pharmacology)
• Dactinomycin (pharmacology)
• Folic Acid (pharmacology)
• Liver Neoplasms (enzymology)
• Male
• Methotrexate (pharmacology)
• Methyltransferases (metabolism)
• Neoplasms, Experimental (enzymology)
• Puromycin (pharmacology)
• Rats
• Tetrahydrofolates (pharmacology)
• Thymidylate Synthase (analysis, metabolism)