Some observations on the reversibility of methotrexate toxicity in normal proliferating tissues.
Thymidine, in the absence of hypoxanthine, failed to protect normal mice from the acute toxicity of methotrexate, though tumor-bearing animals could be protected with thymidine alone, probably as a result of the availability of DNA degradation products released from drug-sensitive tumor cells. Although metrotrexate induced an early purine deficiency in gut cells, this effect was not detected in bone marrow. Later, purine deficiency became apparent in the gut and bone marrow of methotrexate-treated animals.
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D001854:Bone Marrow Cells; D004247:DNA / Q000096:biosynthesis; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D007042:Hypoxanthines / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D002955:Leucovorin / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D011687:Purines / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism; D013936:Thymidine / Q000494:pharmacology
D007042:Hypoxanthines; D011687:Purines; D011743:Pyrimidines; D004247:DNA; D002955:Leucovorin; D013936:Thymidine; D008727:Methotrexate