Spatial and temporal distribution of gamma H2AX fluorescence in human cell cultures following synchrotron-generated X-ray microbeams : lack of correlation between persistent gamma H2AX foci and apoptosis

• Formation of gamma H2AX foci (a marker of DNA double-strand breaks), rates of foci clearance and apoptosis were investigated in cultured normal human fibroblasts and p53 wild-type malignant glioma cells after exposure to high-dose synchrotron-generated microbeams. Doses up to 283 Gy were delivered using beam geometries that included a microbeam array (50 mu m wide, 400 mu m spacing), single microbeams (60-570 mu m wide) and a broad beam (32 mm wide). The two cell types exhibited similar trends with respect to the initial formation and time-dependent clearance of gamma H2AX foci after irradiation. High levels of gamma H2AX foci persisted as late as 72 h post-irradiation in the majority of cells within cultures of both cell types. Levels of persistent foci after irradiation via the 570 mu m microbeam or broad beam were higher when compared with those observed after exposure to the 60 mu m microbeam or microbeam array. Despite persistence of gamma H2AX foci, these irradiation conditions triggered apoptosis in only a small proportion (<5%) of cells within cultures of both cell types. These results contribute to the understanding of the fundamental biological consequences of high-dose microbeam irradiations, and implicate the importance of non-apoptotic responses such as p53-mediated growth arrest (premature senescence).

Subject headings

NATURVETENSKAP  -- Fysik (hsv//swe)

NATURAL SCIENCES  -- Physical Sciences (hsv//eng)

Keyword

microbeam

gamma H2AX

X-rays

radiation therapy

DNA damage

apoptosis

Publication and Content Type

ref (subject category)

art (subject category)