strontium-radioisotopes and Papilloma

We have shown previously that the risk of tumor initiation, promotion, and progression in animals initiated with alkylating agents can be drastically altered by hyperthermia treatments. We show here that ionizing radiation can also alter the risk of tumor initiation by alkylating agents. Using a two-step skin tumorigenesis protocol in female SENCAR mice (initiation by MNNG, promotion with TPA), we exposed the dorsal skin of the mice to various doses of 90Sr/90Y beta radiation near the time of initiation. The radiation produced a dose-dependent reduction in the number of papillomas which appeared after TPA promotion, with about a 20% reduction in animals receiving 0.5 Gy surface dose just before initiation, about 50% reduction after 2.5 Gy, and greater than 80% at doses above 5 Gy. A dose of 2.5 Gy in animals initiated with DMBA produced no significant reduction. One skin hyperthermia treatment (44 degrees C, 30 min) along with radiation in MNNG-initiated animals partially blocked the protective effect of radiation and increased the papilloma frequency. Radiation (2.5 Gy) given either 6 days before or after MNNG initiation was less effective but still reduced papilloma frequency about 20%. In sharp contrast to the marked reduction in papilloma formation, these same animals showed no change in carcinoma frequency with any of the doses or schedules of beta radiation. MNNG initiation alone produced three types of initiated cells. One type, produced in low yield, was promotion-independent with a high probability of progression to a carcinoma and appeared unaffected by the radiation. A second type, produced in intermediate yield, was promotion-dependent and also had a high progression probability, but was likewise unaffected by the radiation. The third and most abundant type was promotion-dependent with a very low progression probability. Radiation exposure resulted in a decrease in the risk of an MNNG initiation event which led only to the third type of cell. The data therefore indicate that the risk of some, but not all, tumor-initiating events caused by alkylating agents can be reduced by an exposure to ionizing radiation.

Topics: Animals; Beta Particles; Carcinoma; Female; Methylnitronitrosoguanidine; Mice; Papilloma; Skin Neoplasms; Strontium Radioisotopes

Female CBA mice were 90Sr-contaminated in utero by amounts ranging from 46 to 740 kBq given to the pregnant dams on the 19th day post coitum. The females were killed at an average age of 10 months. The ovaries were microscopically analysed and morphologic changes were recorded. Multiple corpora lutea were frequent in all but the two highest dose groups. Ovarian cysts were frequent as well. Proliferative events such as hyperplasia of luteinized interstitial cells and down-growths of the germinal epithelium did not occur until a dose of 185 kBq. The findings indicate a non-linear dose-tumor relationship, but also a direct proportion of animals with down-growths and those with tubular adenomas beyond a threshold of 14 per cent.

Topics: Adenoma; Animals; Female; Fetus; Granulosa Cell Tumor; Male; Mice; Mice, Inbred CBA; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Ovarian Neoplasms; Papilloma; Pregnancy; Strontium Radioisotopes