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Chelation of lysosomal iron protects against ionizing radiation.
Division for Biochemistry, Department for Medical Biochemistry and Biophysics, Karolinska Institute, Sweden. Institute for Cinical Cytobiology and Cytopathology, Philipps-Universität, Marburg, Germany . (medicin)
Linköping University, Department of Medicine and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences. (medicin)
Division of Pathology, Department of Laboratory Medicineand Division of Medical Radiation Physics, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden. (medicine)
Division of Pathology, Department of Laboratory Medicineand Division of Medical Radiation Physics, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden. (medicin)
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2010 (English)In: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 432, no 2, 295-301 p.Article in journal (Refereed) Published
Abstract [en]

Ionizing radiation causes DNA damage and consequent apoptosis, mainly due to the production of hydroxyl radicals (HO•) that follows radiolytic splitting of water. However, superoxide (O2•-) and H2O2 also form and induce oxidative stress with resulting LMP (lysosomal membrane permeabilization) arising from iron-catalysed oxidative events. The latter will contribute significantly to radiation-induced cell death and its degree largely depends on the quantities of lysosomal redox-active iron present as a consequence of autophagy and endocytosis of iron-rich compounds. Therefore radiation sensitivity might be depressed by lysosome-targeted iron chelators. In the present study, we have shown that cells in culture are significantly protected from ionizing radiation damage if initially exposed to the lipophilic iron chelator SIH (salicylaldehyde isonicotinoyl hydrazone), and that this effect is based on SIH-dependent lysosomal stabilization against oxidative stress. According to its dose-response-modifying effect, SIH is a most powerful radioprotector and a promising candidate for clinical application, mainly to reduce the radiation sensitivity of normal tissue. We propose, as an example, that inhalation of SIH before each irradiation session by patients undergoing treatment for lung malignancies would protect normally aerated lung tissue against life-threatening pulmonary fibrosis, whereas the sensitivity of malignant lung tumours, which usually are non-aerated, will not be affected by inhaled SIH.

Place, publisher, year, edition, pages
2010. Vol. 432, no 2, 295-301 p.
Keyword [en]
ionizing radiation, iron chelation, lung cancer, lysosome, oxidative stress, salicylaldehyde isonicotinoyl hydrazone (SIH).
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-63266DOI: 10.1042/BJ20100996ISI: 000284813800008PubMedID: 20846118OAI: oai:DiVA.org:liu-63266DiVA: diva2:377374
Note
Original Publication: Carsten Berndt, Tino Kurz, Markus Selenius, Aristi P Fernandes, Margareta R Edgren and Ulf T Brunk, Chelation of lysosomal iron protects against ionizing radiation., 2010, Biochemical Journal, (432), 2, 295-301. http://dx.doi.org/10.1042/BJ20100996 Copyright: Portland Press -- London http://www.portlandpress.com/ Available from: 2010-12-14 Created: 2010-12-14 Last updated: 2017-12-11

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