Mechanisms of Adaptive Responses and Genomic Instability Induced by Low Dose/Low Dose Rate Radiation

摘要

The proposed study investigates the effect of low dose and low dose rate radiation exposure (X-rays) on induced genomic instability and the adaptive response, including the molecular mechanisms for these phenomena. The proposed studies will utilize human cell lines containing a stably integrated plasmid that can be caused by certain kinds of mutational insults to recombine to express the green fluorescent proteins, GFP. The study will use this cell line with the fluorescent plasmid recombination reporter system in a direct study of the effects of 1, 2.5, 5, 7.5, 10, 100 and 500 rads acute X-irradiation and the same doses delivered by protraction at 1 rad or 0.01 rad per minute. This system will be used to provide a quantitative measure of the kinetics of genomic instability in colonies of cells exposed to low dose/dose rate, as well as to examine the adaptive response. The study will also apply micro array technology to investigate the molecular mechanisms underlying induced instability and adaptive effects.