Differences in the biochemical activity in hairless mouse skin and other organs after systemic and topical methotrexate treatment.
DNA synthesis in epidermis, spleen, small intestine, and muscle of the hairless mouse was measured after systemic and topical methotrexate dosing. Mice intraperitoneally injected with methotrexate (5 mg/Kg) incorporated 3H-UdR in epidermis at 90% of baseline at 3 hrs, and the incorporation was not suppressed at 24 hrs. Muscle DNA synthesis was not suppressed. In the spleen and small intestine, incorporation was greatly suppressed to 10% at 3 hrs. On the other hand, after topically applied methotrexate (25 mg/Kg) treatment, epidermis and muscle were 60-90% of baseline at 3-24 hrs and spleen and small intestine were 5-10% at 3-6 hrs. In a prolonged time schedule study (4 days), epidermal incorporation after intraperitoneally applied methotrexate (5 mg/Kg) showed no suppression, but was instead stimulated to 180% at 2 days. 5-Fluorouracil, a thymidine kinase inhibitor in antitumor agents, was topically applied (25 mg/Kg) and compared for DNA synthesis. The incorporation of 3H-UdR was drastically suppressed at 3 hrs. The results suggest that methotrexate is percutaneously absorbed, but does not extensively suppress epidermal DNA synthesis in hairless mice, although it does suppress spleen and intestinal DNA synthesis.
Yoshino
K
K
Maibach
H I
HI
D000287:Administration, Topical; D000818:Animals; D004247:DNA / Q000096:biosynthesis*; D005260:Female; D007274:Injections, Intraperitoneal; D007421:Intestine, Small / Q000378:metabolism*; D008727:Methotrexate / Q000008:administration & dosage*; D051379:Mice; D008812:Mice, Hairless; D012867:Skin / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism*
D004247:DNA; D008727:Methotrexate