Ionizing radiation enhances malignant progression of mouse skin tumors

Chemical carcinogenesis in mouse skin has been divided intothe process of initiation, promotion and progression. Recentlywe have shown that ionizing radiation acts as an initiator inthis model system. In this paper we describe a three-stage experimentusing 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 treatedwith either acetone, TPA (twice a week for 2 weeks) or eightfractions of 1 MeV electrons (1 Gy/fraction over a period of10 days). The conversion of papillomas to squamous cell carcinomaswas 80% for animals treated with ionizing radiation comparedwith 25% for tumor-bearing animals treated with TPA. Ionizingradiation increased the number of cumulative carcinomas pergroup. The lack of an increase in the number of cumulative papillomasper group due to ionizing radiation suggests that the dose andfractionation protocol used in this study enhanced the progressionof pre-existing papillomas.