Characterization of the Long-Term Interaction between Intracellular Reactive Oxygen Species and Oxidative DNA Damage in Murine Lin-/Sca-1+ Cells Exposed to Ionizing Radiation

Abstract

Mutations in the Sfpi1 gene are essential for the development of radia-tion-induced acute myeloid leukemia. In this study, we investigated long-term interaction among immature hematopoietic cell number, intra-cellular reactive oxygen species contents, and oxidative DNA damage fre-quency after irradiation. Lin-/Sca-1+ cells were isolated from C3H/HeN mice on days 1 - 400 after 0 - 3 Gy total body irradiation. On days 1 - 7, the number of surviving cells decreased and reached a minimum; however, the number of cells gradually recovered until day 200. Intracellular reactive oxygen species contents significantly increased from day 1 to day 30. In addition, the frequency of oxidative DNA damage tended to increase from day 1 and day 30, and that at day 30 was significantly increased in the 3 Gy group compared with that in the control group. In contrast, decreased cell number, increased intracellular reactive oxygen species content, and decreased oxidative DNA damage frequency were observed on day 400. These results suggested that oxidative DNA damage was involved in intracellular reactive oxygen species generation induced by cell proliferation to compensate for cell death after irradiation.