Possible Interaction: Methotrexate and S-Adenosylmethionine

“ Methotrexate , a pillar in the treatment of cancer since 1948, decreases SAM levels.”

“At 1 microM, MTX induced differentiation was associated with a marked reduction in the intracellular concentrations of adenosine and, consequently, S-adenosylmethionine (SAM), S-adenosylhomocysteine, polyamines and glutathione (GSH).”

“RESULTS The concentrations of SAM in the CSF were lower in the patients with ALL during treatment with MTX compared with the reference children.”

“ RESULTS The concentrations of SAM in the CSF were lower in the patients with ALL during treatment with MTX compared with the reference children.”

“ MTX treatment alone lowered hepatic concentrations of PCho (to 48% control), GroPCho (to 69% control), betaine (to 55% control), and AdoMet (to 75% control).”

“The addition of MTX treatment to choline deficiency resulted in a larger decrease in AdoMet concentrations (to 75% control) and larger increases in AdoHcy and triacylglycerol concentrations (to 150% and 500% control, respectively) than was observed in choline deficiency alone.”

“In suspension cells but not in adherent cells there was a decrease in the levels of S-adenosylmethionine and polyamines after methotrexate treatment.”

“Depletion of the hepatic SAM pool has likewise been shown to mediate, at least in part, the hepatotoxic effects of ethanol, methotrexate , and niacinamide.”

“Accordingly, both choline deficiency and MTX treatment reduced the AdoMet to AdoHcy ratio.”

“ MTX increased the amount of Hcy about 2-fold in serum, liver and kidney, and decreased the amount of AdoMet in liver and kidney, whereas the AdoHcy content in these tissues was essentially unaffected.”