Chronic toxicity of methotrexate in mice.
Daily (five times/week) administration of 0.25-2 mg methotrexate (MTX)/kg to 5- to 6-week-old male C57BL/6, DBA/2, and C3H mice for 12-18 months was well tolerated, apart from minimal cellular suppression in the lymphoid tissues, testes, and skin. Larger doses of MTX (3-6 mg/kg) given to 5- to 6-week-old mice produced well-known acute to subacute hematopoietic and gastrointestinal damage that leads to early death. These young mice did not develop other lesions that were described in humans after long-term MTX administration, nor was the toxicity cumulative. A large difference was observed in the ability of mice of different ages to withstand the toxic effects of MTX; 16-week-old mice were able to survive daily doses of 3-6 mg/kg up to 18 months. Histologic studies of these mice showed a more pronounced cellular depression of the lymphoid tissues, testes, and skin. Osteoporosis was also observed in these older mice that tolerated the drug for 10 months or longer, thus providing a laboratory animal model for further study of this MTX-induced lesion.
D000367:Age Factors; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001842:Bone and Bones / Q000473:pathology; D004064:Digestive System / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D007248:Infertility, Male / Q000139:chemically induced; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010024:Osteoporosis / Q000139:chemically induced; D011247:Pregnancy; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013045:Species Specificity; D013154:Spleen / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000473:pathology
D008727:Methotrexate