X-ray-induced Transformation and Reversible Suppression of p53 Expression

• Published in: JOURNAL OF RADIATION RESEARCH 1998, Vol.39 (4), p.407-407
• Main Authors: Li chun YANG, Akira TACHIBANA, Yosuke EJIMA, Masao S. SASAKI
• Format: Article
• Language: Japanese
• ISSN: 0449-3060

Cultured mouse cell line m55 is an immortalized cell line retaining several normal characteristics such as near diploid chromosome constitution, contact inhibition at confluence, anchorage dependent growth and responsiveness to EGF. In these cells, X-ray irradiation induces the morphological transformants (TR) in dose-dependent manner. Introduction of a neo-tagged human chromosome 11 reverts these TR cells to the cellular phenotype comparable to the parental m5S cells (RV), which can be again transformed by X-irradiation (RTR). In order to see the genetic control mechanisms associated with the radiation-induced transformation, changes in the expression of p53 gene was studied by Western blotting in these cells. In the parental m5S cells, p53 proteins were constitutively expressed and its accumulation levels changed upon irradiation with 0.02Gy and 3Gy X-rays. However, the expression of p53 was not seen in the TR cells, reappeared by reversion by introducing human chromosome 11 (RV cells), and again disappeared in the transformants (RTR cells) induced by X-irradiation of RV cells. Similarly, RV cells that have lost a human chromosome 11 during culture without G418 also lost the expression of p53. The incubation of TR and RTR cells in the presence of 5-azadeoxycytidine retrieved the expression of p53. These observations strongly suggest the presence of a correlation between transformation and transcriptional silencing of p53, which is regulated by reversible DNA methylation.