Anticarcinogenic methotrexate induces metallothionein synthesis

The structural analogem of folic acid, methotrexate (MTX), acts by condensation with the enzyme dihydrofolate reductase; and here there is proposed the simultaneous mechanism of action of MTX through the formation of a complex with metallothionein (MT). Metallothionein, a low molecular weight protein (Mr ? 6 200), with a great number of cys residues (30%), related with metal homeostasis, could participate through its condensation with MTX and the formation of a chelate with metals MT‐MTX‐Me, in the physiopathological action of MTX. The intestinal mucosa of MTX treated rats and the two anaemic models, iron deficient and posthaemorrhagic anaemia, synthetizes more total proteins, transferrin and cystein (as MT), than in the control animals, by chemical methods. Gel patterns of low relative molecular mass proteins in multisystem PAGE 20% T, 2% CBis in cylindrical tubes under reduced conditions with thioglycolic acid, corroborates the before‐mentioned results. The formation of the complex MT‐MTX‐Me, with the b...