Diminished toxicity of methotrexate in CD2F1 mice pretreated with cycloheximide

Cycloheximide at 100 mg/kg administered intraperitoneally to P388 tumor-bearing CD2F1 mice diminished protein synthesis in the liver, spleen, kidneys, lungs, small intestine and P388 tumor 75 min after administration. Six hours after administration all the above tissues except the tumor no longer demonstrated suppression of protein synthesis. The lethal toxicity of single intraperitoneal doses of methotrexate administered at 1, 3 or 6 h after the cycloheximide was diminished. However, no increase in therapeutic index was achieved with this dose schedule in P388 tumor bearing CD2F1 mice.