Long time persistence of residual 53BP1/gamma-H2AX foci in human lymphocytes in relationship to apoptosis, chromatin condensation and biological dosimetry
2011 (English)In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 87, no 7, 736-745 p.Article in journal (Refereed) Published
Purpose: Novel assay for radiosensitivity is based on measurements of residual DNA repair foci produced by several proteins including phosphorylated H2AX (gamma-H2AX), recombinase Rad51 (Rad51) and tumour suppressor p53 binding protein 1 (53BP1), which co-localise with radiation-induced DNA double-strand breaks (DSB). Here, we studied dose-response for residual 53BP1, Rad51, and gamma-H2AX foci in relationship to apoptosis and chromatin condensation in human G(0)-lymphocytes. Materials and methods: Residual foci, apoptosis and condensation of chromatin were studied following irradiation with gamma-rays at doses of 0.5-10 Gy. Results: No clear dose response for residual Rad51 was seen. Residual 53BP1/gamma-H2AX foci remained in human lymphocytes up to four weeks after irradiation. No foci formed during radiation-induced apoptosis. We provide evidence that irreversible apoptotic condensation of chromatin is responsible for arrest of residual foci and preventing de novo focus formation. Similar linear dose dependences up to 2 Gy were observed for the 53BP1/gamma-H2AX foci at all studied time points. At higher doses, saturation and decline were caused by preferential elimination of apoptotic lymphocytes with residual foci. While primary 53BP1 and gamma-H2AX foci almost completely co-localised, co-localisation of residual foci did not exceed 17%, indicating that 53BP1 and gamma-H2AX proteins may remain for different times at the locations of DSB repair. Conclusions: Prolonged persistence of residual 53BP1/gamma-H2AX foci may be used for biological dosimetry within the dose range up to 2 Gy. While foci are not formed during radiation-induced apoptosis in human lymphocytes, elimination of apoptotic cells with residual foci may affect the dose response.
Place, publisher, year, edition, pages
2011. Vol. 87, no 7, 736-745 p.
apoptosis, DNA repair foci, chromatin condensation, human lymphocytes, radiation, biodosimetry
IdentifiersURN: urn:nbn:se:su:diva-66985DOI: 10.3109/09553002.2011.577504ISI: 000292278200010OAI: oai:DiVA.org:su-66985DiVA: diva2:470062
authorCount :32011-12-282011-12-222011-12-28Bibliographically approved