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Enhancing Nuclear Safety


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The role of oxidative stress in the development of radiation-induced cellular effects: application to accidental localized irradiation.

Carine LAURENT, doctorate thesis of the University of Versailles Saint-Quentin-en-Yvelines, Speciality: Biology, defended on the 7th October 2005.

Document type > *Mémoire/HDR/Thesis

Keywords > deposition, cutaneous injuries, radio-induced inflammation, nuclear workers

Research Unit > IRSN/DRPH/SRBE/LDB

Authors > LAURENT Carine

Publication Date > 07/10/2005

Summary

The mechanisms involved in the happening of late radiation-induced cutaneous injuries are still misunderstood. Several theories were proposed among which, we focused on stromal hypothesis. The latter theory considers DNA damage accumulation in parenchymal cells as responsible for delayed mitotic death. In this respect, oxidative stress might be a major process at the origin of these DNA lesions. However, there was no direct evidence of its presence in cutaneous tissue exposed to high doses of radiation. We demonstrated in a preliminary study the presence 3 months after irradiation, of highly damaged cells in the cutaneous tissue excised from a victim of a radiological accident. Moreover, another in vivo study showed the presence of oxidative phenomena in skin of rats locally exposed to X-rays and a strong decrease in dermal SOD activity associated to the presence of inflammatory process. These phenomena were linked to cutaneous symptoms observed at early times after irradiation. In vitro studies performed on primary cultures of dermal fibroblasts and endothelial cells indicated that radicals were still produced several weeks after irradiation. A delayed increase in micronuclei frequency and in H2AX phosphorylation was observed in irradiated cells and was associated to a decrease in DNA-PKcs expression. Moreover, stress induced-premature senescence (SIPS) was also observed in both irradiated cell types. Antioxidant combination pentoxifylline/trolox, was shown to be protective for dose of 3 Gy whereas it was toxic at irradiation doses of 10 Gy with an emphasized increase in micronuclei and double-strand breaks formation. This was associated to a decrease in DNA-PKcs level. In addition a modulation cell-type dependant of signalling pathways involved in SIPS was also observed.


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