Estrogen enhanced cell-cell signalling in breast cancer cells exposed to targeted irradiation

The influence of estrogen and anti-estrogen treatments on the bystander response was determined by individually irradiating a fraction of cells within the population with a precise number of helium-3 using a charged particle microbeam. Damage was scored as chromosomal damage measured as micronucleus formation.A bystander response measured as increased yield of micronucleated cells was triggered in both MCF-7 and MDA-MB-231 cells. The contribution of the bystander response to total cell damage in MCF-7 cells was higher than that in MDA-MB-231 cells although the radiosensitivity of MDA-MB-231 was higher than MCF-7. Treatment of cells with 17β-estradiol (E2) increased the radiosensitivity and the bystander response in MCF-7 cells, and the effect was diminished by anti-estrogen tamoxifen (TAM). E2 also increased the level of intracellular reactive oxygen species (ROS) in MCF-7 cells in the absence of radiation. In contrast, E2 and TAM had no influence on the bystander response and ROS levels in MDA-MB-231 cells. Moreover, the treatment of MCF-7 cells with antioxidants eliminated both the E2-induced ROS increase and E2-enhanced bystander response triggered by the microbeam irradiation, which indicates that ROS are involved in the E2-enhanced bystander micronuclei formation after microbeam irradiation.The observation of bystander responses in breast tumour cells may offer new potential targets for radiation-based therapies in the treatment of breast cancer.The radiation-induced bystander effect is the appearance of a biological response in nonirradiated cells neighbouring irradiated cells [1]. The response has been demonstrated in cultured cells and tissues by using different irradiation approaches including low fluences of α-particles [2,3], γ-rays [4,5], heavy ions [6,7], and targeted microbeams which allow cells to be individually irradiated through either the nucleus or cytoplasm [8-10]. Many endpoints have been reported for the bystander responses, including DNA dama