Application of 84 µg of actinomycin D inhibits skin tumor formation initiated by either 7,12-dimethylbenz[a]anthracene (DMBA) or β-propiolactone (BPL). Treatment with this dose of actinomycin D inhibits the binding of DMBA to skin DNA by 40%, but does not affect BPL binding to DNA. Inhibition of binding of initiators to DNA cannot explain more than a small part of the inhibition of tumor formation by actinomycin D. A dose of 10 µg of actinomycin D inhibits tumor formation by 40–50% when given the same day as the initiator (DMBA or BPL) or 1 or 7 days later. Application of this dose of actinomycin D inhibited RNA synthesis only slightly for about 12 hours (6–18 hours after treatment), but inhibited DNA synthesis by 75–90% for at least 2 days (from 24–72 hours after treatment). The inhibition of tumor formation by actinomycin D may be related to its inhibition of the incorporation of thymidine-3H into skin DNA. It is not known whether this block of DNA synthesis is reversible or irreversible in potential tumor cells.
This work was supported in part by grants from the American Cancer Society (E-6), the Alexander and Margaret Stewart Trust Fund, and the USPHS (CRTY-5002).