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Inhibition of epidermal DNA synthesis by cycloheximide and other inhibitors of protein synthesis.

Cycloheximide, pactamycin and tenuazonic acid inhibit protein synthesis in eukaryotic cells. It is the purpose of these studies to determine whether these agents would be effective in vivo inhibitors of epidermal DNA synthesis. Single I.P. administration of 1.5 mg/kg cycloheximide, 0, 1 or 3 hours prior to a 45 minute pulse of thymidine-3H inhibited epidermal DNA synthesis by 68%, 63% and 88%, respectively. This response was dose related at 3.75 hours after cycloheximide with no effect at 0.375 mg/kg and maximal inhibition at 1.5 mg/kg. Epidermal DNA synthesis was inhibited 18, 29 and 62% at doses of 1.5, 3.0 and 6.0 mg/kg pactamycin administered 3 hours before thymidine-3H. Similarly, at doses of 70 and 140 mg/kg tenuazonic acid, epidermal DNA synthesis was inhibited by 50% and 60%, respectively. These data suggest the possible use of protein synthesis inhibitors in epidermal disorders.