Protection against Radiation-Induced Carcinogenesis

Division Of Basic Sciences - Nci

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Abstract

Two strains of mice are being used in this project. Female C3H and CBA mice were exposed to a total body dose of radiation of 3 Gy with or without Tempol supplementation in the animal's food. Immediately following the radiation exposure, animals will be placed on either control or Tempol-containing food. The groups include: a) no radiation, control food, b) 3 Gy, control food, c) no radiation, Tempol food, and d) 3 Gy, Tempol food. For C3H mice, one additional group was added receiving 3 Gy total body irradiation where the administration of the Tempol containing food was delayed one month post-irradiation. Preliminary data show that Tempol treatment provided a statistically significant survival advantage to both mouse strains. Tempol administered to animals one month post-radiation also provided a statistically different survival advantage. For the C3H mice Tempol treatment delayed and reduced the incidence of radiation-induced lymphoma. Pathology data for CBA mice is not yet available. These preliminary data would encourage further research with Tempol as a chemopreventive agent. The hypothesis is also being tested that mice protected from lethal total body irradiation by administration of a radioprotector immediately before radiation exposure will experience an elevated risk of cancer induction. Mice were exposed to a total body radiation dose of 10.8 Gy, a radiation dose that results in 100% lethality. Ten minutes prior to the 10.8 Gy exposure the animals will be injected with a radioprotector. The control for this group, another set of animals was exposed to 5.4 Gy total body irradiation. This radiation dose was derived from the radiation dose modification factor (2) when the radioprotector is administered 10 min before total body irradiation. These animals will also be followed for their entire lifespan for tumor induction as outlined above. Preliminary data show that the survival of animals receiving 5.4 Gy is similar to animals receiving 10.8 Gy with the radioprotector. Pathology data is not yet available.