Thymidylate synthetase activity in the Novikoff hepatoma

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 a...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1976-12, Vol.36 (12), p.4500-4503
Main Authors: Roth, J J, Roth, J S
Format: Article
Language:English
Subjects:
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
Thymidylate Synthase - metabolism
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0008-5472