Inter-individual and inter-cell type variation in residual DNA damage after in vivo irradiation of human skin |
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Authors: | Melvin Lee Kiang Chua,Navita SomaiahSara Bourne,Frances DaleyRoger A&rsquo Hern,Otilia NutaSue Davies,Carsten HerskindAnn Pearson,Jim WarringtonSarah Helyer,Roger OwenJohn Yarnold,Kai Rothkamm |
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Affiliation: | a Health Protection Agency, Chilton, UK b Gray Institute for Radiation Oncology and Biology, Oxford, UK c The Institute of Cancer Research and The Royal Marsden Hospital, Sutton, UK d University Medical Centre Mannheim, University of Heidelberg, Germany e Gloucestershire Oncology Centre, Cheltenham, UK |
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Abstract: | PurposeThe aim of this study was to compare inter-individual and inter-cell type variation in DNA double-strand break (DSB) repair following in vivo irradiation of human skin.Materials and methodsDuplicate 4 mm core biopsies of irradiated and unirradiated skin were collected from 35 patients 24 h after 4 Gy exposure using 6 MeV electrons. Residual DSB were quantified by scoring 53BP1 foci in dermal fibroblasts, endothelial cells, superficial keratinocytes and basal epidermal cells.ResultsCoefficients of inter-individual variation for levels of residual foci 24 h after in vivo irradiation of skin were 39.9% in dermal fibroblasts, 44.3% in endothelial cells, 32.9% in superficial keratinocytes and 46.4% in basal epidermal cells (p < 0.001, ANOVA). In contrast, the coefficient of inter-cell type variation for residual foci levels was only 11.3% in human skin between the different epidermal and dermal cells (p = 0.034, ANOVA). Foci levels between the different skin cell types were correlated (Pearson’s R = 0.855-0.955, p < 0.001).ConclusionsPatient-specific factors appear to be more important than cell type-specific factors in determining residual foci levels following in vivo irradiation of human skin. |
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Keywords: | DNA double-strand break Inter-individual variation Inter-cell type variation In vivo irradiation Human skin |
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