[Gene rearrangement and radiation carcinogenesis]

Abstract

In view of the elevated risk of leukemia among A-bomb survivors, genetic alterations associated with Leukemia can be considered to have been induced by ionizing radiation. Therefore, to clarify this possibility, an examination was made to see whether genetic changes such as BCR-ABL translocation closely associated with chronic myelogenous leukemia (CML) are actually induced by radiation. BCR-ABL translocation is easily detected by means of reverse transcription polymerase chain reaction. One hundred million cells of the promyelocytic leukemia-derived cell line HL60, which do not have such a gene rearrangement, were irradiated with 100 Gy of X-ray, after which RNA was extracted and examined for any rearrangements of BCR and ABL genes. Five kinds of bands were observed in the HL60 cells irradiated with 100 Gy of X-ray, and it became clear that these positive bands contain both BCR gene and ABL gene by the direct sequencing method. Furthermore, these gene rearrangements included not only the rearrangements specifically identified with CML but also atypical rearrangements which are not generally observed clinically. The induction by X-irradiation of such gene changes characteristic of malignant tumors, which are closely associated with radiation carcinogenesis, suggests that they are the initial gene changes in radiation carcinogenesis.