DNA methylation during mouse hemopoietic differentiation and radiation-induced leukemia

Giotopoulos, G., McCormick, C., Cole, C., Zanker, A., Jawad, M., Brown, R. and Plumb, M. (2006) DNA methylation during mouse hemopoietic differentiation and radiation-induced leukemia. Experimental Hematology, 34(11), pp. 1462-1470. (doi: 10.1016/j.exphem.2006.06.008)

Abstract

Objective To examine DNA methylation in mouse hemopoiesis before and after in vivo exposure to a leukemogenic dose of x-rays, and address whether methylation levels are associated with the relative radiosensitivity of tissues in vivo. Methods The methylation status of control CBA/H and C57BL/6 mouse tissues before and after exposure to 3-Gy x-rays, and myeloid and lymphoid leukemias and lymphomas, was assessed by the direct analysis of the 5-methylcytosine (5-MeC) content of DNA, and by Southern blot analysis of genomic repeat sequences. Results The DNA 5-MeC content of bone marrow is 15% lower than spleen. Together with the analyses of stem (myeloid) and progenitor (lymphoid) leukemias and lymphomas, we found a trend of increasing methylation during hemopoietic differentiation. Exposure to x-rays induced greater cell death in the hypomethylated bone marrow (>80%) than spleen (50%) in vivo, supporting the observed correlation found between methylation status and radiosensitivity of other high-turnover hierarchical tissues. Furthermore, there was an 8% DNA 5-MeC content decrease in bone marrow after in vivo exposure to 3-Gy x-rays, but this was genotype dependent, being observed in AML-susceptible (CBA/H) but not AML-resistant (C57BL/6) inbred mice. Conclusion Together these data suggest that methylation status may be related to the relative radiosensitivity of high-turnover hierarchical tissues such as bone marrow and that radiation-induced DNA hypomethylation has a role in radiation leukemogenesis

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Brown, Prof Robert and McCormick, Mrs Carol
• Authors: Giotopoulos, G., McCormick, C., Cole, C., Zanker, A., Jawad, M., Brown, R., and Plumb, M.
• College/School: College of Medical Veterinary and Life Sciences
• Journal Name: Experimental Hematology
• Journal Abbr.: Exp. Hematol.
• ISSN: 0301-472X
• Published Online: 14 October 2006