Detection of Minimal Malignant Clone in Lymphocytes and Bone Marrow Cells by Cytogenetic and Molecular Genetic Studies in Healthy Atomic Bomb Survivors

Abstract

In order to assess the minimal malignant clone (MMC) for the development of leukemia, we studied the bone marrow and lymphocytes of total 44 healthy atomic - bomb survivors by cytogenetic technique. In the cytogenetic study, we compared the frequencies of chromosome aberration and quality of chromosome aberrations detected in the bone marrow and peripheral lymphocytes from 13 and 39 samples from 44 healthy atomic bomb survivors, respectively, relevant to the nonrandom aberrations prevalent in the human leukemic and malignant lymphoma cells. The frequencies of chromosome aberrations in bone marrow cells were slightly lower than those in lymphocytes and a few percent of clone were found in both bone marrow and lymphocytes. Although the completely same type chromosome aberrations as those found in leukemia and lymphomas were not observed, out of 3,846 cells with chromosome aberrations found in 52 samples for 44 survivors, 35 percent were related to the sites of oncogenes involving in the leukemogenesis and lymphomagenesis such as 8q24, 9q34 and 22q11. In addition, molecular genetic studies using PCR techniques for RAS point mutations in 3 survivors, specific chromosome translocations such as t(14;18), and t(7;14) in the bone marrow and peripheral lymphocytes of 3 healthy survivors revealed that any MMC was detected. On the other hand, by in vivo selection assay could detect transforming genes of N-and K-RAS in bone marrow samples from all 4 survivors. Three of the 4 survivors had development cancer or leukemia 7-10 years after present examination. Even though, we couldn't detect any MMC by chromosome analysis, the finding that 20 fragile sites were correlated with higher number of breakpoint of 52 atomic bomb survivors might also significantly an important role MMC in the initiation of radiation-related leukemogenesis and lymphomagenesis process, as seen presently, there is still an increase in the development