Ionizing radiation enhances malignant progression of mouse skin tumors

Chemical carcinogenesis in mouse skin has been divided into the process of initiation, promotion and progression. Recently we have shown that ionizing radiation acts as an initiator in this model system. In this paper we describe a three-stage experiment using ionizing radiation in the third stage of mouse skin carcinogenesis. CD-1 mice were initiated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) followed by biweekly promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). After 20 weeks of promotion, the animals were treated with either acetone, TPA (twice a week for 2 weeks) or eight fractions of 1 MeV electrons (1 Gy/fraction over a period of 10 days). The conversion of papillomas to squamous cell carcinomas was 80% for animals treated with ionizing radiation compared with 25% for tumor-bearing animals treated with TPA. Ionizing radiation increased the number of cumulative carcinomas per group. The lack of an increase in the number of cumulative papillomas per group due to ionizing radiation suggests that the dose and fractionation protocol used in this study enhanced the progression of pre-existing papillomas.