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Open Access Research

Radiation induced apoptosis and initial DNA damage are inversely related in locally advanced breast cancer patients

Beatriz Pinar12, Luis Alberto Henríquez-Hernández23*, Pedro C Lara12, Elisa Bordon2, Carlos Rodriguez-Gallego24, Marta Lloret12, Maria Isabel Nuñez5 and Mariano Ruiz De Almodovar5

Author Affiliations

1 Radiation Oncology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Spain

2 Instituto Canario de Investigación del Cáncer (ICIC), Spain

3 Clinical Sciences Department, Universidad de Las Palmas de Gran Canaria, Spain

4 Immunology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Spain

5 Radiology Department, Hospital Universitario San Cecilio, Universidad de Granada, Spain

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Radiation Oncology 2010, 5:85  doi:10.1186/1748-717X-5-85

Published: 24 September 2010

Abstract

Background

DNA-damage assays, quantifying the initial number of DNA double-strand breaks induced by radiation, have been proposed as a predictive test for radiation-induced toxicity. Determination of radiation-induced apoptosis in peripheral blood lymphocytes by flow cytometry analysis has also been proposed as an approach for predicting normal tissue responses following radiotherapy. The aim of the present study was to explore the association between initial DNA damage, estimated by the number of double-strand breaks induced by a given radiation dose, and the radio-induced apoptosis rates observed.

Methods

Peripheral blood lymphocytes were taken from 26 consecutive patients with locally advanced breast carcinoma. Radiosensitivity of lymphocytes was quantified as the initial number of DNA double-strand breaks induced per Gy and per DNA unit (200 Mbp). Radio-induced apoptosis at 1, 2 and 8 Gy was measured by flow cytometry using annexin V/propidium iodide.

Results

Radiation-induced apoptosis increased in order to radiation dose and data fitted to a semi logarithmic mathematical model. A positive correlation was found among radio-induced apoptosis values at different radiation doses: 1, 2 and 8 Gy (p < 0.0001 in all cases). Mean DSB/Gy/DNA unit obtained was 1.70 ± 0.83 (range 0.63-4.08; median, 1.46). A statistically significant inverse correlation was found between initial damage to DNA and radio-induced apoptosis at 1 Gy (p = 0.034). A trend toward 2 Gy (p = 0.057) and 8 Gy (p = 0.067) was observed after 24 hours of incubation.

Conclusions

An inverse association was observed for the first time between these variables, both considered as predictive factors to radiation toxicity.