$1.25 million Grant from the National Aeronautics and Space Administration (NASA)
Research: My laboratory studies the effects and underlying mechanisms of low dose ionizing radiation in normal human cells, with particular interest in the radiation-induced bystander effect and the radiation-induced adaptive response.
Abdelrazek Ahmed Bedi, PhD
Sonia Deltoledo, PhD
Ph.D., 1995, University of Ottawa, Canada M.Sc., 1989, University of Manitoba, Canada B.Sc., 1973, University of Calgary, Canada
Edouard I. Azzam, Sonia M. de Toledo and John B. Little (2003) Gap-Junctions, Oxidative Metabolism and the Ionizing Radiation Induced Bystander Effect. Oncogene 22 , 7050-7057. ybobra.ru
Edouard I. Azzam, Sonia M. de Toledo and John B. Little (2003) Expression of CONNEXIN43 Is Highly Sensitive to Ionizing Radiation and other Environmental Stresses. Cancer Res. 63 , 7128-7135.
Edouard I. Azzam, Sonia M. de Toledo, Douglas R. Spitz and John B. Little (2002) Oxidative Metabolism Modulates Signal Transduction and Micronucleus Formation in Bystander Cells from a-Particle-Irradiated Normal Human Fibroblast Cultures. Cancer Res. 62 , 5436-5442.
Edouard I. Azzam, Sonia M. de Toledo and John B. Little (2001) Direct Evidence for the Participation of Gap-Junction Mediated Intercellular Communication in the Transmission of Damage Signals from a-Particle Irradiated to Non-irradiated Cells. Proc. Natl. Acad. Sci. USA, 98 , 473-478 .
E.I. Azzam, S.M. de Toledo, G.P. Raaphorst and R.E.J. Mitchel (1996) Low-dose ionizing radiation decreases the frequency of neoplastic transformation to a level below the spontaneous rate in C3H 10T1/2 cells. Radiat. Res. , 146 , 369-373.
Effects and Underlying Mechanisms of Low Dose Ionizing Radiation in Normal Human Cells
A large volume of laboratory and human epidemiological studies have shown that high doses of ionizing radiation engender significant health risks. The underlying mechanisms of these radiation effects are fairly well elucidated. In contrast, the risks of low doses remain ambiguous. A major goal of our research has been to define low dose induced biological effects in model mammalian cells, and to investigate specific molecular/biochemical events associated with the expression of these effects.
Following exposure to low dose/low fluence ionizing radiation, two cellular responses that can impact risk have been observed. In cell populations exposed to fluences of a-particles (a high linear energy transfer radiation) by which a very small fraction of the cells is traversed by a particle track, stress, including genetic effects, occur in both the irradiated and neighboring non-irradiated cells. The occurrence of such ?bystander effects' has been suggested to amplify the harmful effects of radiation. In contrast, cells that are exposed to low dose, low linear energy transfer radiation (e.g. g-rays) become resistant to the damaging effects of a subsequent challenge dose of ionizing radiation or other oxidizing agents. Such adaptive responses are thought to mitigate the harmful effects of radiation. While evidence for both adaptive and bystander effects has been well established, a clear understanding of the basic biochemical and molecular processes by which they occur is only beginning to emerge.