Origin of Radiation Carcinogenesis is Chromosome Aneuploidy

概要

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It has been believed that the first target of radiation carcinogenesis is DNA. However, this is not proved for radiation carcinogenesis yet. We discovered that frequency of aneuploid cell was closely related to that of radiation-induced cell transformation and natural cell transformation by high-density cultivation, but gene mutation was not. Cell with p53 gene becomes tetraploid, but does not get tumorigenicity. On the other hand, cells without p53 gene function become a triploid easily, and acquire tumorigenicity. Both radiation exposure and high-density cultivation elevated the level of intracellular oxidative radicals. These radicals induced centrosome destabilization and produced cells carrying extra centrosome, which promote merotelic attachment of chromosome by altering spindle geometry. Unresolved merotelic attachments can give rise to lagging chromosomes at anaphase. Aneuploidy was seen in high frequency in early process of cell transformation. These results strongly suggest that a main target of carcinogenesis by low dose radiation is not DNA, but is centrosome, which are the proteins to constitute chromosomal homeostasis maintenance mechanism. In addition, this route may be the same as that of natural carcinogenesis. These serial results support necessity of a review of a LNT hypothesis at a radioprotective point of view.
日本保健物理学会の論文