Correlation between the radiation responses of fibroblasts cultured from individual patients and the risk of late reaction after breast radiotherapy

Otilia Nuta; Navita Somaiah; Sue Boyle; Melvin Lee Kiang Chua; Lone Gothard; John Yarnold; Kai Rothkamm; Carsten Herskind

doi:10.1016/j.canlet.2016.02.036

Correlation between the radiation responses of fibroblasts cultured from individual patients and the risk of late reaction after breast radiotherapy

Otilia Nuta, Navita Somaiah, Sue Boyle, Melvin Lee Kiang Chua, Lone Gothard, John Yarnold, Kai Rothkamm, Carsten Herskind^*

^*Corresponding author for this work

Public Health England

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

Late normal tissue toxicity varies widely between patients and limits breast radiotherapy dose. Here we aimed to determine its relationship to DNA damage responses of fibroblast cultures from individual patients. Thirty-five breast cancer patients, with minimal or marked breast changes after breast-conserving therapy consented to receive a 4 Gy test irradiation to a small skin field of the left buttock and have punch biopsies taken from irradiated and unirradiated skin. Early-passage fibroblast cultures were established by outgrowth and irradiated in vitro with 0 or 4 Gy. 53BP1 foci, p53 and p21/CDKN1A were detected by immunofluorescence microscopy. Residual 53BP1 foci counts 24 h after in vitro irradiation were significantly higher in fibroblasts from RT-sensitive versus RT-resistant patients. Furthermore, significantly larger fractions of p53- but not p21/CDKN1A-positive fibroblasts were found in cultures from RT-sensitive patients without in vitro irradiation, and 2 h and 6 d post-irradiation. Exploratory analysis showed a stronger p53 response 2 h after irradiation of fibroblasts established from patients with severe reaction. These results associate the radiation response of fibroblasts with late reaction of the breast after RT and suggest a correlation with severity.

Original language	English
Pages (from-to)	324-330
Number of pages	7
Journal	Cancer Letters
Volume	374
Issue number	2
DOIs	https://doi.org/10.1016/j.canlet.2016.02.036
Publication status	Published - 1 May 2016

Bibliographical note

Funding Information:
This study was supported by grant number 06049 from the Royal Marsden Hospital Charity, UK , and by the NIHR Centre for Research in Health Protection .

Funding Information:
We thank Ms. N. Guerth for excellent technical assistance with establishment of fibroblast cultures and performance of immunocytochemistry (Ki-67, p53, p21/CDKN1A). The Royal Marsden Hospital Charity is gratefully acknowledged for financial support. We acknowledge NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and the ICR and to the Centre for Research in Health Protection at Public Health England. Dr. Melvin Chua is kindly supported by the National Medical Research Council Singapore Transition Award (NMRC/TA/0030/2014).

Keywords

53BP1
Breast cancer
Double-strand breaks
Individual radiosensitivity
Normal-tissue reaction
P53

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.canlet.2016.02.036

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title = "Correlation between the radiation responses of fibroblasts cultured from individual patients and the risk of late reaction after breast radiotherapy",

abstract = "Late normal tissue toxicity varies widely between patients and limits breast radiotherapy dose. Here we aimed to determine its relationship to DNA damage responses of fibroblast cultures from individual patients. Thirty-five breast cancer patients, with minimal or marked breast changes after breast-conserving therapy consented to receive a 4 Gy test irradiation to a small skin field of the left buttock and have punch biopsies taken from irradiated and unirradiated skin. Early-passage fibroblast cultures were established by outgrowth and irradiated in vitro with 0 or 4 Gy. 53BP1 foci, p53 and p21/CDKN1A were detected by immunofluorescence microscopy. Residual 53BP1 foci counts 24 h after in vitro irradiation were significantly higher in fibroblasts from RT-sensitive versus RT-resistant patients. Furthermore, significantly larger fractions of p53- but not p21/CDKN1A-positive fibroblasts were found in cultures from RT-sensitive patients without in vitro irradiation, and 2 h and 6 d post-irradiation. Exploratory analysis showed a stronger p53 response 2 h after irradiation of fibroblasts established from patients with severe reaction. These results associate the radiation response of fibroblasts with late reaction of the breast after RT and suggest a correlation with severity.",

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author = "Otilia Nuta and Navita Somaiah and Sue Boyle and Chua, {Melvin Lee Kiang} and Lone Gothard and John Yarnold and Kai Rothkamm and Carsten Herskind",

note = "Funding Information: This study was supported by grant number 06049 from the Royal Marsden Hospital Charity, UK , and by the NIHR Centre for Research in Health Protection . Funding Information: We thank Ms. N. Guerth for excellent technical assistance with establishment of fibroblast cultures and performance of immunocytochemistry (Ki-67, p53, p21/CDKN1A). The Royal Marsden Hospital Charity is gratefully acknowledged for financial support. We acknowledge NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and the ICR and to the Centre for Research in Health Protection at Public Health England. Dr. Melvin Chua is kindly supported by the National Medical Research Council Singapore Transition Award (NMRC/TA/0030/2014). ",

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AU - Rothkamm, Kai

AU - Herskind, Carsten

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Correlation between the radiation responses of fibroblasts cultured from individual patients and the risk of late reaction after breast radiotherapy

Abstract

Bibliographical note

Keywords

UN SDGs

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