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.”

“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.”

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