Title

Synchrotron photoactivation of cisplatin elicits an extra number of DNA breaks that stimulate RAD51-mediated repair pathways

RIS ID

76642

Publication Details

corde, s., Balosso, J., Elleaume, H., Renier, M., Joubert, A., Biston, M., Adam, J., Charvet, A., Brochard, T., Le Bas, J., Esteve, F. & Foray, N. (2003). Synchrotron photoactivation of cisplatin elicits an extra number of DNA breaks that stimulate RAD51-mediated repair pathways. Cancer Research, 63 3221-3227.

Abstract

Combination of cis-platinum with ionizing radiation is one of the most promising anticancer treatments that appears to be more efficient than radiotherapy alone. Unlike conventional X-ray emitters, accelerators of high energy particles like synchrotrons display powerful and monochromatizable radiation that makes the induction of an Auger electron cascade in cis-platinum molecules [also called photoactivation of cis-platinum (PAT-Plat)] theoretically possible. Here, we examined the molecular consequences of one of the first attempts of synchrotron PAT-Plat, performed at the European Synchrotron Research Facility (Grenoble-France). PATPlat was found to result in an extra number of slowly repairable DNA double-strand breaks, inhibition of DNA-protein kinase activity, dramatic nuclear relocalization of RAD51, hyperphosphorylation of the BRCA1 protein, and activation of proto-oncogenic c-Abl tyrosine kinase.

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