Eman Mohammed Elbakrawy1,2, Ammar Mayah1, Mark A Hill3, Munira Kadhim1. 1. Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford OX3 0BP, UK. 2. Department of Radiation Physics, National Center for Radiation Research and Technology, Atomic Energy Authority, 3 Ahmed El-Zomor Al Manteqah Ath Thamenah, Nasr City, Cairo 11787, Egypt. 3. Gray Laboratories, MRC Oxford Institute for Radiation Oncology, University of Oxford, ORCRB Roosevelt Drive, Oxford OX3 7DQ, UK.
Abstract
PURPOSE: To study the induction of genomic instability (GI) in the progeny of cell populations irradiated with low doses of alpha-particles and the potential role of exosome-encapsulated bystander signalling. METHODS: The induction of GI in HF19 normal fibroblast cells was assessed by determining the formation of micronuclei (MN) in binucleate cells along with using the alkaline comet assay to assess DNA damage. RESULTS: Low dose alpha-particle exposure (0.0001-1 Gy) was observed to produce a significant induction of micronuclei and DNA damage shortly after irradiation (assays performed at 5 and 1 h post exposure, respectively). This damage was not only still evident and statistically significant in all irradiated groups after 10 population doublings, but similar trends were observed after 20 population doublings. Exosomes from irradiated cells were also observed to enhance the level of DNA damage in non-irradiated bystander cells at early times. CONCLUSION: very low doses of alpha-particles are capable of inducing GI in the progeny of irradiated cells even at doses where <1% of the cells are traversed, where the level of response was similar to that observed at doses where 100% of the cells were traversed. This may have important implications with respect to the evaluation of cancer risk associated with very low-dose alpha-particle exposure and deviation from a linear dose response.
PURPOSE: To study the induction of genomic instability (GI) in the progeny of cell populations irradiated with low doses of alpha-particles and the potential role of exosome-encapsulated bystander signalling. METHODS: The induction of GI in HF19 normal fibroblast cells was assessed by determining the formation of micronuclei (MN) in binucleate cells along with using the alkaline comet assay to assess DNA damage. RESULTS: Low dose alpha-particle exposure (0.0001-1 Gy) was observed to produce a significant induction of micronuclei and DNA damage shortly after irradiation (assays performed at 5 and 1 h post exposure, respectively). This damage was not only still evident and statistically significant in all irradiated groups after 10 population doublings, but similar trends were observed after 20 population doublings. Exosomes from irradiated cells were also observed to enhance the level of DNA damage in non-irradiated bystander cells at early times. CONCLUSION: very low doses of alpha-particles are capable of inducing GI in the progeny of irradiated cells even at doses where <1% of the cells are traversed, where the level of response was similar to that observed at doses where 100% of the cells were traversed. This may have important implications with respect to the evaluation of cancer risk associated with very low-dose alpha-particle exposure and deviation from a linear dose response.
Authors: M A Kadhim; S J Marsden; D T Goodhead; A M Malcolmson; M Folkard; K M Prise; B D Michael Journal: Radiat Res Date: 2001-01 Impact factor: 2.841
Authors: James Milner; Clive Shrubsole; Payel Das; Benjamin Jones; Ian Ridley; Zaid Chalabi; Ian Hamilton; Ben Armstrong; Michael Davies; Paul Wilkinson Journal: BMJ Date: 2014-01-10