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.

1

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).

This content is only available via PDF.