Chronic exposure to ionizing radiation as a tumor promoter in mouse skin.

We have tested chronic exposure to 90Y beta radiation for its action as a complete tumor promoter, a stage I tumor promoter, or a stage II tumor promoter in SENCAR mouse skin. In skin initiated with a single application of 7,12,dimethylbenz[a]anthracene (DMBA, 10 nmol), chronic exposure to beta radiation as a complete promoter (0.5 Gy, twice/week, 13 weeks) produced no tumors and, when added to a complete chemical promoter (TPA), reduced tumor frequency about 30%. A similar result was observed when beta radiation was tested as a stage II promoter. DMBA-initiated mice that received chemical (12-O-tetradecanoylphorbol-13-acetate, TPA) stage I promotion followed by 13 weeks of beta-radiation exposure (0.5 Gy, twice/week) as stage II promotion produced essentially no tumors, and combining the same chronic beta-radiation exposure with chemical (mezerein) stage II promotion reduced tumor frequency about 20% when compared to a similar group that was not irradiated. Chronic beta-radiation exposure was tested two ways as a stage I tumor promoter in initiated skin that was subsequently treated with mezerein as a stage II promoter. Stage I promotion was shown to proceed with the passage of time, indicating this process occurs naturally in the absence of chemical or physical stimulation. Hyperthermia, previously shown to be a potent inhibitor of chemically stimulated stage I promotion, had no effect on the natural process, indicating at least some differences in mechanism between the two processes. The natural process was, in fact, inhibited by chemical tumor promoters, but not by radiation. In addition to the increase resulting from this natural process, tumor frequency was further increased slightly but significantly (12-15%, P less than or equal to 0.05) when chronic radiation exposure was given as a stage I promoter (0.5 Gy, twice/week, 13 weeks) subsequent to initiation, in spite of the expected 20% reduction resulting from this dose. Exposure of initiated animals to radiation (0.5 or 1.0 Gy, twice/week, 2 weeks) in addition to TPA as stage I promotion produced a similar increase in tumor frequency (P less than 0.02). At higher radiation doses, however, tumor frequency was reduced compared to unirradiated controls. In a third test as a stage I promoter, beta radiation (0.5 Gy twice/week, 4 weeks) was given prior to initiation with N-methyl-N'-nitro-N-nitrosoguanidine in animals subsequently promoted by TPA (twice/week, 13 weeks), and again the radiation slightly but significantly (P less than 0.03) increased tumor frequency compared to the unirradiated control group.(ABSTRACT TRUNCATED AT 400 WORDS)