Host: The Japan Radiation Research Society
In vitro transformation of X-irradiated Syrian/golden hamster embryo (SHE) cells has been examined so far. It was reported that the initial process involves two steps, one is immortalization, and the other is morphological transformation. Recently, it becomes possible to visualize DNA double strand breaks using radiation-induced foci of DNA damage checkpoint factors. We examined early passage of SHE cells and found that they have 3.6 foci of phosphorylated ATM in average. This indicates that endogenous DNA double strand breaks caused by so called "culture stress" might be a cause to inactivate p53 function whose process is indispensable for immortalization of rodent cells. It should be noted that the process involves genetic alterations, but is independent of radiation exposure. Dose-dependent changes were observed in morphology of the colonies formed by cells surviving X-rays. They commonly lost dependency of cell growth on plastic surface, and all the morphologically transformed clones demonstrated loss of a protein whose molecular weight is 240 kDa. This protein was equivalent to a human extracellular matrix protein, tenasin. Thus, it was suggested that suppression of gene transcription could be involved in a down-regulation of tenasin. Such epigenetic mechanism was confirmed by the introduction of the reporter gene into rodent cells. These results indicate that both genetic and epigenetic mechanisms are involved in neoplastic transformation of X-irradiated SHE cells, however, radiation only plays a role in the latter step. As radiation-induced deletions result in a large scale of chromatin remodeling, it is likely a cause of epigenetic suppression of gene functions.
