Effect of methotrexate with 5-methyltetrahydrofolate rescue and dietary homocystine on survival of leukemic mice and on concentrations of liver adenosylamino acids.
We have increased significantly the survival time of DBA/2 mice bearing methionine-dependent L1210 or L5178Y leukemia cells by i.p. administration of lethal doses of methotrexate (five daily doses of 25 mg/kg body weight) followed by rescue with 5-methyl tetrahydrofolate (five daily doses of 20 mg/kg body weight). The mice were maintained on a semipurified choline- and cyst(e)ine-free diet containing 0.32% L-methionine. We further increased significantly the survival time of the treated animals bearing L5178Y cells, but not those bearing L1210 cells, by substitution of 0.86% DL-homocystine for the methionine in the diet. We have examined the effects of both diets in mice treated with methotrexate and 5-methyl tetrahydrofolate, singly and in combination, on the concentrations of S-adenosylmethionine and S-adenosylhomocysteine in the liver, a tissue highly active in the metabolism of these amino acids. The substitution of homocystine for methionine in the diet of untreated animals led to a significant increase in S-adenosylhomocysteine and decrease in S-adenosylmethionine in the liver, with a resultant profound decrease in the ratio of S-adenosylmethionine to S-adenosylhomocysteine which was not further altered significantly by administration of methotrexate.
D000818:Animals; D004032:Diet; D006710:Homocysteine / Q000031:analogs & derivatives*; D006711:Homocystine / Q000008:administration & dosage / Q000627:therapeutic use*; D007700:Kinetics; D007939:Leukemia L1210 / Q000188:drug therapy*; D007940:Leukemia L5178 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D051379:Mice; D008811:Mice, Inbred DBA; D012435:S-Adenosylhomocysteine / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism*; D013763:Tetrahydrofolates / Q000627:therapeutic use*
D013763:Tetrahydrofolates; D006710:Homocysteine; D006711:Homocystine; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; C005984:5-methyltetrahydrofolate; D008727:Methotrexate