Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury

Abstract

Cellular exposure to ionizing radiation leads to oxidizing events that alter atomic structure through direct interactions of radiation with target macromolecules or via products of water radiolysis. Further, the oxidative damage may spread from the targeted to neighboring, non-targeted bystander cells through redox-modulated intercellular communication mechanisms. To cope with the induced stress and the changes in the redox environment, organisms elicit transient responses at the molecular, cellular and tissue levels to counteract toxic effects of radiation. Metabolic pathways are induced during and shortly after the exposure. Depending on radiation dose, dose-rate and quality, these protective mechanisms may or may not be sufficient to cope with the stress. When the harmful effects exceed those of homeostatic biochemical processes, induced biological changes persist and may be propagated to progeny cells. Physiological levels of reactive oxygen and nitrogen species play critical roles in many cellular functions. In irradiated cells, levels of these reactive species may be increased due to perturbations in oxidative metabolism and chronic inflammatory responses, thereby contributing to the long-term effects of exposure to ionizing radiation on genomic stability. Here, in addition to immediate biological effects of water radiolysis on DNA damage, we also discuss the role of mitochondria in the delayed outcomes of ionization radiation. Defects in mitochondrial functions lead to accelerated aging and numerous pathological conditions. Different types of radiation vary in their linear energy transfer (LET) properties, and we discuss their effects on various aspects of mitochondrial physiology. These include short and long-term in vitro and in vivo effects on mitochondrial DNA, mitochondrial protein import and metabolic and antioxidant enzymes.

Drosophila MelanogasterShow a Threshold Effect in Response to Radiation

“…Our data seem to be consistent with the existence of a protective effect, but are not conclusive. It is tempting to speculate that one may see a protective effect in other measures such as behavior.The physiological responses inferred from our gene expression study (Table 3) are consistent with the oxidative theory of radiation damage (Bokov et al 2004;Azzam et al 2012): radiation damages cells by creating reactive oxygen species and other oxidizing agents that damage cell components, in addition to direct damage from the radiation. Perturbations in oxidative metabolism, including oxidative phosphorylation (oxphos) Endocytosis and the sulfur relay system are types of transport, which are affected by oxidative damage to lipid bilayers in the cell membrane (Azzam et al 2012).…”

“…This suggests that the effects seen at later days could be due to chronic effects of oxidative stress, possibly from continuous generation of reactive oxygen species as described in Azzam et al (2012).…”

Cancer, Oxidative Stress, and Metastasis

“…Cellular ROS levels can also increase as a result of UV irradiation, ionizing radiation, toxins such as heavy metals, chemotherapy, and neighboring inflammatory cells, although the mechanisms vary widely (Federico et al 2007;Azzam et al 2012;Vera-Ramirez et al 2012). For example, the chemotherapeutic doxorubicin forms a complex with topoisomerase and DNA that leads to double-strand breaks, increasing ROS levels and potentiating cellular damage (Lyu et al 2007;Rowe et al 2008;Zhang et al 2012).…”

NADPH oxidase DUOX1 promotes long-term persistence of oxidative stress after an exposure to irradiation

“…The persistence of such effects in progeny cells has profound implications for long-term health risks, including emergence of a second malignancy after radiotherapy (1). The thyroid gland is one of the most sensitive organs to the carcinogenetic effects of IR.…”