Inhibition of tumor induction in two-stage carcinogenesis on mouse skin.

SUMMARY The inhibition of tumorigenesis by various agents possessing known biochemical and/or biologic effects has been examined using mouse skin initiation-promotion experiments. The agents were applied on mouse skin at various time intervals with respect to the initiating treatment with 7,1 2-dimethylbenz(a)-anthracene. Actinomycin D and aflatoxin B1 were most effec tive 30 and 7 days after initiation respectively. On the other hand, dl-diepoxybutane and acridine orange were most effec tive when applied at the time of initiation. The different agents probably act by several mechanisms, and the same agent may inhibit tumorigenesis in different ways depending on the time of application with respect to initiation. It is proposed that actinomycin D interferes selectively with initiated or pre neoplastic cells and that initiation represents a complex se quential biochemical process.