Croton Oil Enhancement of Skin Tumor Initiation by N-Methyl-N′-Nitro-N-Nitrosoguanidine: Possible Role of DNA Replication

Summary An application of 0.5% croton oil at times from 6 hr before until 24) hr after initiation with 4 μmoles MNNG led to a threefold increase in papilloma yield and a substantial shortening of the latent period in two-stage tumor induction experiments in mouse skin. Since DNA replication was not stimulated by croton oil until 2-4 days after application of MNNG, this enhancement cannot be explained by an increased uptake of the MNNG by DNA-synthesizing cells or by increased susceptibility of these cells. If DNA replication is involved in initiation, then our results suggest that the critical DNA replication occurs after the interaction of MNNG with DNA, but before the initial damage can be repaired, perhaps resulting in a nonrepairable mutation.