Involvement of ATP in radiation-induced bystander effect as a signaling molecule

Abstract

We previously reported that low doses (0.25-0.5 Gy) of γ-rays induce intracellular antioxidant, radioresistant, DNA damage repair, and so on. Meanwhile, we have recently reported that ATP is released from the cells exposed to low-dose γ-rays. Here, it was investigated whether or not g-radiation-induced release of extracellular ATP contributes to various radiation effects, in paricular, focusing on the inductions of intracellular antioxidant and DNA damage repair. Irradiation with γ-rays or exogenously added ATP increased expression of intracellular antioxidants such as thioredoxin and the increases were blocked by pretreatment with an ecto-nucleotidase in both cases. Moreover, release of ATP and autocrine/paracrine positive feedback through P2Y receptors serve to amplify the cellular repair response to radiation-induced DNA damage. To sum up, it would be suggested that ATP signaling is important for the effective induction of radiation stress response, such as protection of the body from the radiation and DNA damage repair. In addition, the possibility that this signaling is involved in the radiation resistance of cancer cells and beneficial effect on the organism of low-dose radiation and radiation adaptive response, would be further suggested. © 2014 The Pharmaceutical Society of Japan.