Heterogeneity of ?H2AX Foci Increases in Ex Vivo Biopsies Relative to In Vivo Tumors.

ABSTRACT: The biomarker for DNA double stand breaks, gammaH2AX (?H2AX), holds a high potential as an intrinsic radiosensitivity predictor of tumors in clinical practice. Here, two published ?H2AX foci datasets from in and ex vivo exposed human head and neck squamous cell carcinoma (hHNSCC) xenografts were statistically re-evaluated for the effect of the assay setting (in or ex vivo) on cellular geometry and the degree of heterogeneity in ?H2AX foci. Significant differences between the nucleus areas of in- and ex vivo exposed samples were found. However, the number of foci increased linearly with nucleus area in irradiated samples of both settings. Moreover, irradiated tumor cells showed changes of nucleus area distributions towards larger areas compared to unexposed samples, implying cell cycle alteration after radiation exposure. The number of residual ?H2AX foci showed a higher degree of intra-tumoral heterogeneity in the ex vivo exposed samples relative to the in vivo exposed samples. In the in vivo setting, the highest intra-tumoral heterogeneity was observed in initial ?H2AX foci numbers (foci detected 30 min following irradiation). These results suggest that the tumor microenvironment and the culture condition considerably influence cellular adaptation and DNA damage repair.

SUBMITTER: Rassamegevanon T 

PROVIDER: S-EPMC6163410 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature