Role of oxidatively-induced DNA damage and inflammation in radiation long term effects and carcinogenesis

Abstract

Ionizing radiation is undoubtedly the most frequently used means of cancer treatment especially in the case of solid tumors like breast, prostate etc. Significant evidence suggests that long-term effects of radiation in patients who have undergone even successful treatment include high oxidative stress and inflammation in their blood and various tissues and the underestimation of the so called "non-targeted" effects. This chronic stress can lead in some cases to malignant transformation (secondary primary cancers) after radiation treatment of primary tumors several years after the initial irradiation. This mini-review discusses the evidence for the role(s) of oxidative DNA damage and inflammation as one of the primary contributing factors in chronic tissue injury and secondary carcinogenesis. Several important questions arise like for example if based on this idea we can develop in vivo reliable predictive biomarkers for radiation-induced chronic injury and to pinpoint carcinogenesis precursor sites after radiotherapy treatment even years after the patient exposure.

Basal levels of glutathione peroxidase correlate with onset of radiation induced lung disease in inbred mouse strains

“…The pathogenesis of the radiation-induced lung diseases is not yet mechanistically understood (5,13), but it is known that radiation therapy produces reactive oxygen species (ROS), which, if not neutralized, can result in the altered function or death of cells through oxidative damage to proteins, lipids, and DNA (2,7,20,25,35). Oxidative damage to DNA can be measured by production of 8-hydroxydeoxyguanosine , which is the most abundantly generated DNA oxidation product following radiation exposure (36).…”