Target of Radiation Carcinogenesis Is Protein: Becoming Triploid Is Proximate Cause of Cell Transformation

Abstract

Although numerical chromosome aberration is closely related to expression of malignant transformation, it is not clear how a change of chromosome number occurs. Here we propose that aneuploidy, which is ubiquitous in cancer and inevitably unbalances thousands of synergistic genes, destabilizes the structure of chromosomes. We obtained primary cells from embryos of the p53 wild-type and p53 knockout (KO) mouse and cultured the cells by 5T10 culture protocol. Both types of cells were easily immortalized, and immortalized p53 wild-type cells became a tetraploid population and immortalized p53 KO cells became a triploid population. In addition, only immortalized p53 KO cells showed tumorigenicity at around 30 passages, but p53 wild-type cells did not do so, even at more than 100 passages. These results strongly suggest that aneuploidy is the cause rather than a consequence of carcinogenesis. Loss of p53 function promotes derivation of aneuploidy closely.