Inter-individual and inter-cell type variation in residual DNA damage after in vivo irradiation of human skin

Melvin Lee Kiang Chua, Navita Somaiah, Sara Bourne, Frances Daley, Roger A'Hern, Otilia Nuta, Sue Davies, Carsten Herskind, Ann Pearson, Jim Warrington, Sarah Helyer, Roger Owen, John Yarnold, Kai Rothkamm

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20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)225-230
Number of pages6
JournalRadiotherapy and Oncology
Volume99
Issue number2
DOIs
Publication statusPublished - May 2011

Bibliographical note

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.

Keywords

  • DNA double-strand break
  • Human skin
  • In vivo irradiation
  • Inter-cell type variation
  • Inter-individual variation

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