TY - JOUR
T1 - Inter-individual and inter-cell type variation in residual DNA damage after in vivo irradiation of human skin
AU - Chua, Melvin Lee Kiang
AU - Somaiah, Navita
AU - Bourne, Sara
AU - Daley, Frances
AU - A'Hern, Roger
AU - Nuta, Otilia
AU - Davies, Sue
AU - Herskind, Carsten
AU - Pearson, Ann
AU - Warrington, Jim
AU - Helyer, Sarah
AU - Owen, Roger
AU - Yarnold, John
AU - Rothkamm, Kai
N1 - Funding Information:
This study was funded by The Royal Marsden NHS Foundation Trust Charity Panel , Grant No. 06048 and the NIHR Centre for Research in Health Protection at the Health Protection Agency . The authors would also like to acknowledge NHS funding to the NIHR Biomedical Research Centre. This report is work commissioned by the National Institute for Health Research. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.
Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/5
Y1 - 2011/5
N2 - Purpose: The 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 methods: Duplicate 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. Results: Coefficients 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). Conclusions: Patient-specific factors appear to be more important than cell type-specific factors in determining residual foci levels following in vivo irradiation of human skin.
AB - Purpose: The 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 methods: Duplicate 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. Results: Coefficients 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). Conclusions: Patient-specific factors appear to be more important than cell type-specific factors in determining residual foci levels following in vivo irradiation of human skin.
KW - DNA double-strand break
KW - Human skin
KW - In vivo irradiation
KW - Inter-cell type variation
KW - Inter-individual variation
UR - https://www.scopus.com/pages/publications/79958137942
UR - https://www.scopus.com/pages/publications/79958137942#tab=citedBy
U2 - 10.1016/j.radonc.2011.04.009
DO - 10.1016/j.radonc.2011.04.009
M3 - Article
C2 - 21620495
AN - SCOPUS:79958137942
SN - 0167-8140
VL - 99
SP - 225
EP - 230
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
IS - 2
ER -