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.