PURPOSE: To establish and characterize an in vitro model of radiation-induced transformation of normal glial cells. MATERIALS AND METHODS: During the last week of gestation, pregnant Sprague-Dawley rats were either irradiated at 3.5 Gy (0.022 Gy h(-1)) with a 60Co source or sham irradiated. On day 21 of gestation, cortical nerve cells from foetuses were isolated, and then maintained in culture for about 100 passages, in presence of 10(-9) g/ml of tetradecanoyl phorbol acetate (TPA). To follow transformation, various parameters: cell type, proliferation, clonogenicity, karyotypes and tumorigenicity, were studied at different passages. RESULTS: As the number of passages increased, control cells lost their glial morphology and were immortalized. They kept on expressing specific markers of type 2 astrocytes (glial fibrillary acid protein (GFAP) and A2B5). Karyotypes remained near diploid. At all passages tested, they were not tumorigenic in nude mice. Irradiated cells expressed the 2A progenitor cell specific markers: GFAP, vimentin and A2B5. Karyotypes evolved toward polyploidy and cells displayed an iso 7 and a marker. These changes were synchronous with modifications in tumorigenicity. Metastases were even observed in nude mice. CONCLUSIONS: Cells from irradiated animals were fully transformed, while cells from sham irradiated animals were only immortalized.
PURPOSE: To establish and characterize an in vitro model of radiation-induced transformation of normal glial cells. MATERIALS AND METHODS: During the last week of gestation, pregnant Sprague-Dawley rats were either irradiated at 3.5 Gy (0.022 Gy h(-1)) with a 60Co source or sham irradiated. On day 21 of gestation, cortical nerve cells from foetuses were isolated, and then maintained in culture for about 100 passages, in presence of 10(-9) g/ml of tetradecanoyl phorbol acetate (TPA). To follow transformation, various parameters: cell type, proliferation, clonogenicity, karyotypes and tumorigenicity, were studied at different passages. RESULTS: As the number of passages increased, control cells lost their glial morphology and were immortalized. They kept on expressing specific markers of type 2 astrocytes (glial fibrillary acid protein (GFAP) and A2B5). Karyotypes remained near diploid. At all passages tested, they were not tumorigenic in nude mice. Irradiated cells expressed the 2A progenitor cell specific markers: GFAP, vimentin and A2B5. Karyotypes evolved toward polyploidy and cells displayed an iso 7 and a marker. These changes were synchronous with modifications in tumorigenicity. Metastases were even observed in nude mice. CONCLUSIONS: Cells from irradiated animals were fully transformed, while cells from sham irradiated animals were only immortalized.
Authors: Raymund L Yong; Chunzhang Yang; Jie Lu; Huaien Wang; Cody D Schlaff; Anita Tandle; Christian A Graves; Abdel G Elkahloun; Xiaoyuan Chen; Zhengping Zhuang; Russell R Lonser Journal: Nat Commun Date: 2014-12-17 Impact factor: 14.919