Response of methylenetetrahydrofolate levels to methotrexate in Krebs ascites cells

Publisher Website
Google Scholar
Abstract
Levels of methylenetetrahydrofolate in Krebs ascites [mouse tumor] cells subsequent to transplantation and the effects of methotrexate on these levels were measured. To directly measure methylenetetrahydrofolate in tissue extracts, the cofactor was incorporated into a covalent ternary complex with thymidylate synthase and 3H-labeled fluoro-dUMP. A 3- to 4-day lag preceded rapid growth of the tumor cells; this same kinetic behavior was observed for methylenetetrahydrofolate levels in the tumor cells. Liver and kidney tissue from the same animals also showed an increase in methylenetetrahydrofolate in the tumor cells depended upon concentration and the post-transplantation time at which treatment was initiated. Levels of methylenetetrahydrofolate in the tumor cells were most sensitive to the drug at the beginning of the rapid growth phase and were more sensitive to a given level of methotrexate in the presence of phospholipids. A slight but significant increase in methylenetetrahydrofolate occurred in some cases in response to the presence of methotrexate.