Cell cycle dependent DNA break increase in ataxia telangiectasia lymphoblasts after radiation exposure

Abstract

The most striking feature of ataxia telangiectasia (AT) cells is their profound sensitivity to ionising radiation. A deficiency in the rejoining of radiation induced DNA breaks has been suggested to be responsible for AT radiosensitivity; however, the existing literature is controversial. A subpopulation, which is present in irradiated AT lymphoblasts, but rarely in controls, has been reported previously. The cells that make up this subpopulation harbour highly fragmented DNA and are responsible for the overall increase in DNA breaks soon after irradiation in AT lymphoblasts. This study examines the influence of the cell cycle on the highly damaged subpopulation. The frequency of highly damaged cells was highest when AT lymphoblasts were irradiated during the G2/M phase. In contrast, AT lymphoblasts irradiated during the G0/G1 phase displayed a frequency similar to control cells. Thus, only G2/M and to some extent S phase cells contribute to an increased DNA break number in AT lymphoblasts early after irradiation. These findings might explain several inconsistencies reported in the literature. (J Clin Pathol: Mol Pathol 2001;54:347-350)

Alteration Analysis of Bone Marrow Mesenchymal Stromal Cells from De Novo Acute Myeloid Leukemia Patients at Diagnosis

“…Moreover, quiescence of blast cells by direct contact with MSCs (N-MSCs or auto and hetero LMSCs) was associated with a slight decrease in anti-gH2AX staining (a marker of DNA DSBs) compared with MSC-free cultures (P < 0.01) (Fig. 7E), consistent with the previously reported relationship between DNA damage level and cell cycle entry [29].…”

“…DNA from MSC was extracted with the Genomic DNA from Tissue kit (Macherey-Nagel Dueren, Germany) according to the manufacturer's recommendations. MSC telomere length was measured by Southern blot analysis of terminal restriction fragments as previously described [29].…”

Role of cell cycle in mediating sensitivity to radiotherapy

“…From work with synchronized populations of cells, it is clear that radiation-induced chromosomal damage and micronuclei formation depend on the cell cycle distribution. Ionizing radiation can produce both different types of, and quantitative differences in, chromosomal aberrations at various stages of the cell cycle (222,224,226). Illustrating the latter point, in Chinese hamster cells, the frequency of chromosomal aberrations after irradiation was about three times greater for G 2 phase cells than for S and G 1 phase cells (227).…”

Ataxia-Telangiectasia Mutated Modulation of Carbon Metabolism in Cancer

“…ATM is the primary gene mutation in ataxia telangiectasia (A-T) ( 18 , 19 ). A-T is primarily documented as an immunodeficiency and neuronal degeneration disorder affecting 1:40,000–1:100,000 people worldwide ( 18 , 20 ).…”