title: Differences in the biochemical activity in hairless mouse skin and other organs after systemic and topical methotrexate treatment.
abstract: 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.
authors.forename: K
authors.initials: K
authors.lastname: Yoshino
authors.forename: H I
authors.initials: HI
authors.lastname: Maibach
mesh_terms: 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*
chemical_list: D004247:DNA; D008727:Methotrexate