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Topical Application of Actinomycin D on Mouse Skin: Effect on the Synthesis of Ribonucleic Acid and Protein

Carcinogenesis Studies Branch, National Cancer Institute, Bethesda, Maryland

Topical application of actinomycin D inhibits the synthesis of RNA in mouse skin. The maximum inhibition obtained was approximately 75% and was distributed uniformly throughout the interfollicular and follicular epidermal cells. This inhibition was produced by dosage levels which ranged from 1 µg of actinomycin administered once to 15 µg given 6 times every 3 hr. Regardless of the dosage level used, the layer of cells closest to the surface of skin was always inhibited within a shorter period following the topical application of actinomycin D than were the deeper lying cells. Inhibition required 2–3 days to reach a uniform level throughout the epidermis. The duration of inhibition (5–11 days), however, was dependent upon the dosage level applied. Evidence is presented which shows that topical applications of actinomycin D function only locally and do not alter RNA metabolism in either the untreated areas of skin or systemic organs. Inhibition of RNA synthesis as considered at the molecular level is not random but instead appears to be highly specific for ribosomal RNA. However, the possibility that messenger RNA was also inhibited, but to an immeasurable extent, was not eliminated. Protein synthesis, as measured by the incorporation of leucine-³H into skin protein, was not significantly altered by a low dosage level of actinomycin (1 µg). Application of a high level (15 µg administered 6 times), however, produced an increase in rate of leucine uptake (35% by 4 days). Alterations in the mitotic index of interfollicular cells, as well as hyperplasia, were observed at the higher dosage level.

Received 11/ 5/65.