Inter-strain variation of skin reaction among three strains of mice after fractionated irradiation.

[Purpose]To clarify the mechanism the heterogeneity in the response to ionizing irradiation arising from a genetic variation between individual humans, we here investigated the irradiated skin reaction of mice fractionated irradiation with comparison of the results after single dose irradiation setting.[Material and Method]Female mice, 12 weeks old of the inbred strains C3H/HeMs, C57BL/6J, A/J were used through experiments. After Cs-137 gamma rays irradiated 10 fraction- 3, 4, 5, 6 Gy/ 12 days on right-hind legs, and comparison of fractionated irradiation with single dose. [Results]1. Radiosensitivity of a group of fractionated radiation was C3H/HeMs< A/J< C57BL/6J. 2. Latent periods appeared the same point in a group of single dose, but a group of fractionated radiation was different among three strains or irradiated dose. 3. Peak skin reaction score was exhibited dose dependency, although fractionated irradiation groups was low compared with single dose groups, the strain difference was not observed in each irradiation group. But low dose was not displayed dose dependency, the strain difference observed.[Discussion] Inter-strain differences were observed in radiation susceptibility among three strains of mice using the functional endpoint of skin reaction after local fractionated irradiation. In particular, peak skin reaction score in latent periods and low dose observed strain difference.日本放射線影響学会第４６回大

Inter-strain variation of apoptotic index of jejunal crypts between mouse systems after gamma ray whole body irradiation

In the clinic, interindividual differences in normal tissue response to radiotherapy have been observed and genetic factors are suggested to be responsible for this variation. Murine models have proven to be useful for the study of cytotoxic agents including radiation on the jejunum. We here report three murine strain differences in the levels of radiation-induced apoptosis in jejunal crypt cells. The apotosis positivity cell in jejunum carried out apoptosis index comparatively, and radiation susceptibility of strains was evaluated. Apoptosis index in C3 H/Hem was consistently lower than in A/J, or C57BL/6J at various times up to 24 hr after irradiation with 0.5 Gy. (P< 0.05). There was no difference among three strains after irradiation with 5 Gy. In the frequency of appearance of an apoptosis cell, C57BL/6J and A/J were radiation quantity susceptibility as compared with C3 H/Hem.日本放射線影響学会第４６回大

Strain dependent differences in a histological study of CD44 and collagen fibers with an expression analysis of inflammatory response related genes in irradiated murine lung

Using a mouse model, we investigated the mechanisms of heterogeneity in response to ionizing radiation in this research. C57BL/6J and C3H/HeMs mice were irradiated with gamma rays at 10 and 20 Gy. The animals were sacrificed at times corresponding to the latent period, the pneumonic phase, and the start of the fibrotic phase for histological investigation. Small areas of fibrosis initially appeared in C57BL/6J mice at 4 weeks postirradiation with 20 Gy, whereas small inflammatory lesions appeared at 4 and 8 weeks after 20 and 10 Gy, respectively. The alveoli septa were thickened by an infiltration of inflammatory cells, and alveoli were obliterated in lungs from C57BL/6J mice after 20 Gy irradiation. At 24 hours and from 2 to 4 weeks postirradiation, fourfold more CD44 positive cells had accumulated in the lungs of C3H/HeMs than in C57BL/6J mice. Hyaluronan accumulated 12 hours after irradiation, and the rapid resolution was achieved within 2 weeks in the lungs in both strains of mice. C57BL/6J mice lungs accumulated dense collagen at 8 weeks. Quantitative RT-PCR assay was performed for several genes selected by cDNA microarray analysis. The expression of several genes, such as Cap1, Il18, Mmp12, Per3, Ltf, Ifi202a, and Rad51ap1 showed strain-dependent variances. In conclusion, a histological investigation suggested that C3H/HeMs mice were able to induce a more rapid clearance of matrix after irradiation than C57BL/6J mice. The expression analysis showed that the several genes are potentially involved in interstrain differences in inflammatory response causing radiation-induced lung fibrosis

Fractionated irradiation augments inter-strain variation of skin reactions among three strains of mice

The multifraction regimens commonly used in conventional clinical radiotherapy are largely based on radiobiological experiments. However, no experimental reports on skin reactions focusing on inter-strain differences have displayed clinical relevance to the fractionated dose schedule. In this study, mice of inbred strains A/J, C57BL/6J, and C3H/HeMs were used to reveal inter-strain difference after multifractionated irradiation. Irradiation was performed daily at graded doses of 30-60 Gy total doses, with 10 fractions of 3-6 Gy. Acute skin reactions following irradiation were scored for 50 days after irradiation. Dividing a dose into a number of fractions obviously spared skin damage in the three strains of mice. No mouse exhibited a skin damage score more than 1.5, while single dose irradiation resulted in skin damage scores up to 3. The three different strains, however, showed varying susceptibility to fractionated irradiation within the range under 1.5. C3H/HeMs did not display any skin reaction after irradiation with 40 Gy total dose, while C57BL/6J and A/J demonstrated various skin reactions. Different latent periods of damage were also observed among the strains after irradiation at each dose. Our data suggest that genetic factors cause obvious variations in severity of damage and latent period after fractionated irradiation