Ionizing radiation as an initiator: Effect of proliferation and promotion time on tumor incidence

To investigate the effect of the proliferative state of the skin prior to irradiation and the promotion duration after irradiation on tumor incidence, 12-0-tetradecanoyl phorbol 1-13-acetate (TPA, 17 nmol) was applied to one half of the mice 24 hr prior to X-rays. The skin of CD-1 mice was irradiated using 4 MeV X-rays at a dose rate of 0.31 Gy/min. Animals received a single dose of X-rays at 0.5 Gy or 11.25 Gy followed by twice weekly applications of TPA (8 nmol). Animals were promoted for either 10 or 60 wk and followed for 80 wk after initiation. All animals that were promoted with TPA for the same duration had a similar incidence of papillomas regardless of radiation or TPA pretreatment. Promotion time altered the incidence of squamous cell carcinomas (SCC) at the 0.5 Gy initiation dose regardless of TPA pretreatment. In contrast, at 11.25 Gy there was no difference in the SCC incidence in animals that were promoted for 10 vs 60 wk. TPA pretreatment at the higher dose resulted in an overall decrease in tumor incidence. AT 11.25 Gy and 10 wk of promotion we observe a similar SCC incidence as compared to 0.5 Gy and 60 wk of promotion. These data support earlier findings that radiation can act as a weak initiator of SCC and suggest that TPA and ionizing radiation are acting in a similar manner to induce tumors in mouse skin