Emerging role of radiation induced bystander effects: Cell communications and carcinogenesis

Extensive epidemiological and toxicological research over several decades has focused on the health effects of radiation to understand the risk of exposure to both public and workforce. Ionizing radiation has been used in both diagnostic and therapeutic medical applications and described as a double-edged sword [1]. However, there are considerable concerns about the detrimental health effects associated with direct radiation exposure [1-3] even on metabolically inactive cells [4,5]. Radiation is harmful in terms of risks to health from accidental exposure and its role as a carcinogen [6], however on the other side it is beneficial for the use of various diagnostic and therapeutic procedures such as the treatment of cancer. Radiotherapy (RT) continues to be an important therapeutic modality for the treatment of cancer. RT for cancers allows killing of the cancer cells but also shows a risk for adverse consequences such as tissue atrophy and formation of secondary tumors at the same organ, or at some distanced part of body [7]. Furthermore, radiation exposure during diagnostic (e.g. X-rays, CT-scans) and RT procedures shows varying health effects in the general population and also in cancer patients [8-14]. But with cancer survivors living longer, there is a growing concern regarding the risk of radiation-induced secondary cancers in patients treated with ionizing radiation. The situation is important for children, who are inherently more radiosensitive and therefore at greater risk for radiation induced post-radiotherapy cancer development [15-17].The DNA damage response system, which maintains the survival and genomic stability of the cell, represents a vital line of defense against various exogenous and endogenous DNA damaging agents [18]. Radiation can induce apoptosis or trigger DNA repair mechanisms. In general minor DNA damage is thought to halt cell cycle to allow effective repair, while more severe damage can induce an apoptotic cell death program. Until rela