Oxidative stress levels and dynamic changes in mitochondrial gene expression in a radiation-induced lung injury model.

Zhongyuan Yin,Qiong Wang,Guanghai Yang,Sisi Deng

doi:10.1093/jrr/rry105

Zhongyuan Yin, Qiong Wang + Show 2 more

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https://doi.org/10.1093/jrr/rry105

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Abstract

The purpose of this study was to set up a beagle dog model, for radiation-induced lung injury, that would be able to supply fresh lung tissues in the different injury phases for research into oxidative stress levels and mitochondrial gene expression. Blood serum and tissues were collected via CT-guided core needle biopsies from dogs in the various phases of the radiation response over a 40-week period. Levels of reactive oxygen species (ROS) and manganese superoxide dismutase 2 (MnSOD) protein expression in radiation-induced lung injury were determined by in situ immunocytochemistry; malondialdehyde (MDA) content and reductase activity in the peripheral blood were also tested; in addition, the copy number of the mitochondrial DNA and the level of function of the respiratory chain in the lung tissues were assessed. ROS showed dynamic changes and peaked at 4 weeks; MnSOD was mainly expressed in the Type II alveolar epithelium at 8 weeks; the MDA content and reductase activity in the peripheral blood presented no changes; the copy numbers of most mitochondrial genes peaked at 8 weeks, similarly to the level of function of the corresponding respiratory chain complexes; the level of function of the respiratory chain complex III did not peak until 24 weeks, similarly to the level of function of the corresponding gene Cytb. Radiation-induced lung injury was found to be a dynamically changing process, mainly related to interactions between local ROS, and it was not associated with the levels of oxidative stress in the peripheral blood. Mitochondrial genes and their corresponding respiratory chain complexes were found to be involved in the overall process.

Highlights

60% of all cancer patients receive radiotherapy at some point during the course of their disease, and late toxicity to normal tissues limits the radiation dose that can be applied to the tumor
A key factor in determining the state of oxidative stress is the presence of reactive oxygen species (ROS), which can interact with bases, ribose and phosphodiester linkages and can cause deoxyribonucleic acid (DNA) damage and subsequent apoptosis [6]
Each time we were able to obtain 25–30 μg of lung-tissue specimens from the site of exposure using Computed tomography (CT)-guided techniques for the lung biopsy

Summary

Introduction

60% of all cancer patients receive radiotherapy at some point during the course of their disease, and late toxicity to normal tissues limits the radiation dose that can be applied to the tumor. Tolerable doses are often linked to suboptimal tumor control, in addition to side effects that lead to decreased quality of life; for example, radiation-induced pneumonitis and fibrosis are dose-limiting side effects of thoracic irradiation [1,2,3,4]. Considerable progress has been made during the last decade with respect to the discovery of the involved effector cells and soluble mediators, the determination of the network of pathophysiological events and the cellular cross-talk that links acute tissue damage to chronic inflammation and fibrosis still requires further investigation. It has been shown that cellular oxidative stress plays an important role in radiation-induced lung injury (RILI), and oxidative stress can be used as a monitoring index for the development, progression and prognosis of RILI [5]. A growing number of studies have demonstrated that mitochondria are important sites

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