1Department of Radiation Oncology, Yonsei University Medical College, Seoul, Korea. 2Yonsei Cancer Center, Seoul, Korea. 3Yonsei Medical Research Center, Seoul, Korea.
ABSTRACT
PURPOSE: To characterize strain-specific differences in radiation response in murine tissues with different radiosensitivity.
MATERIALS AND METHODS: Six-week old male mice of 2 strains, C57Bl/6J and C3H/HeJ, were given whole body gamma-radiation with a single dose of 10 or 25 Gy. At different times after irradiation, mice were killed and tissues with different radiosensitivity, thymus and liver, were collected. Each tissue sample was stained with hematoxylin and eosin and apoptotic cells were scored. Expression of p53, Bcl-2, Bcl-x, and Bax was analysed by western blotting and densitometry.
RESULTS: Radiation induced massive apoptosis in thymus with a peak level at 8 h after radiation. With 10 Gy irradiation, apoptotic indices in C57Bl/6J and C3H/HeJ were 81.0 2.5% and 59.4 4.0%, respectively (p<0.05). Radiation upregulated the expression of p53, Bcl-x, and Bax, but not Bcl-2; p53 with a peak level of 2.5 fold (C57Bl/6J) and 1.4 fold (C3H/HeJ) at 4 h, Bax with a peak level of 2.6 fold (C57Bl/6J) and 1.3 fold (C3H/HeJ) at 8 h, and Bcl-x with a peak level of 11.1 fold (C57Bl/6J) and 8.2 fold (C3H/HeJ) at 8 h after radiation. In liver, however, radiation-induced apoptosis was minimal (peak apoptotic index of 2.1% in C57Bl/6J and 1.7% in C3H/HeJ). None of p53, Bcl-2, Bcl-x, and Bax was significantly increased.
CONCLUSIONS: Induction of apoptosis and regulation of related genes by radiation were tissue specific. Strain difference of radiation-induced apoptosis was well coupled with theinduction of related genes in thymus, a radiosensitive tissue. This study shows that quantitative difference of radiation induced apoptosis by strain is regulated at the gene level with the involvement of multiple genes.
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