45. Analysis of Genetic Differences in Radiation Sensitivity Using Animal Models.

Mayumi Iwakawa, Ryonfa Lee, Miyako Goto, Chisa Ohira, Toshie Ohta, Shuhei Noda, Yoshinobu Harada and Takashi Imai

Keywords: strain difference, radiosensitivity, mouse, jejunal crypt, skin reaction

Analysis of 5 murine strain differences were demonstrated by examining the extent of normal tissue damage from irradiation for several endpoints used in experimental animals. Levels of radiation-induced normal tissue damage were compared in A/J, C57BL, C3H, C3H-scid and C.B-scid mice. Jejunal Crypt Assay: whole body irradiated mice were sacrificed 3.5 days later and the number of regenerating crypts of the sectioned jejunum was scored. Endogenous spleen colony assay: whole body irradiated mice were sacrificed 9 days later and their spleens were removed and the colonies were counted. Acute Skin Reaction: One hind leg of each mouse was irradiated and the skin response was observed. Leg Contracture Assay: The length of irradiated leg and unirradiated leg to the ankle were measured. Early and Late Response of the Lung: the thorax of mice was irradiated. Pathological changes of the lung were observed and fibrogenetic cytokines were measured. C3H mice showed the highest resistance against radiation in most of the assays, while the scid mice were found to be the most sensitive among the four strains analyzed. The inter-strain difference of radiation sensitivity revealed in this study strongly supports the hypothesis that genetic factors are an important determinant for the response against irradiation. A macroarray assay for gene expression is now under investigation.