LOW DOSE RADIATION : A COMPARATIVE BIOCHEMICAL ANALYSIS OF THE LINEAR-NO THRESHOLD AND HORMESIS MODELS By: Malek Elsayyid Mentor: Dr. Eickmeyer With help from: Dr. Bimal DasMahapatra
OVERVIEW Background info LNT argument Hormesis Argument HIF1- α Metabolic shifts Lall & Ganapathy experiment
IONIZING RADIATION DEFINITION: “Ionizing radiation is any type of particle or electromagnetic wave that carries enough energy to ionize or remove electrons from an atom.” Doss, H. M. "Ionizing Radiation and Humans â The Basics." Physics Central. APS Physics. Web. 21 Feb
HOW DOES IONIZING RADIATION AFFECT YOUR DNA? Ionizing waves/particles can break bonds and interact with DNA in two main ways: Directly ionizing DNA molecules, or neighboring molecules which will then ionize DNA. Indirectly, by creating free radicals, which interact with DNA. If particles directly or indirectly interact with DNA molecules, they can damage vital gene sequences. Some of these genes include those responsible for cell replication, which if damaged can cause cells to replicate uncontrollably as seen in Cancer cells.
WHAT ABOUT “LOW DOSE” RADIATION? Three main arguments: 1.Linear-no threshold model 2.Threshold model 3.??????????? Radiation Hormesis
GRAPHS OF MODELS
AREA OF CONTROVERSY LNT model uses epidemiological data and extrapolates damage to health of low doses from high dose data. Oka, Yoshiaki. "The Fukushima Daiichi Nuclear Plant Accident Caused by the Massive Tsunami." The Great East Japan Earthquake:Opinion:WASEDA ONLINE. The Japan News. Web. 22 Feb
RADIATION DOSE UNITS rad (short for radiation absorbed d ose) 100 rad = one Joule/kilogram (J/kg) = 1 Gray (Gy) (Q) = quality factor of the radiation Rem = rad x Q 100 rem = 1 Sv Sv = Gy x Q Sievert is the equivalent dose Gray is a measure of deposition of energy in tissue. Multiply equivalent dose by weighting factor of tissue to get effective dose
LINEAR HYPOTHESIS More logic based than actual data Defines a dose as an average of 1 photon going through 1 nucleus Only looks at a single cell, isolated from the rest of the tissue Assumes that the same biological process is affected at dose D 1 as well as D 1/10
QUESTION! How many of you were productive over spring break? As much as you are right now, towards the end of the semester? How did you feel after finals last semester?
HORMESIS HYPOTHESIS “The background exposure to which all organisms are subjected throughout evolutionary time.” “Stress-derived radiation hormesis arising as a protective mechanism derived from metabolic adaptation to environmental stresses throughout evolutionary time especially from climate-based extremes.” Hypoxia induced Factor 1 alpha (HIF-1-α )- Transcription factor is activated in low oxygen levels (thus the hypoxia). IR causes ROS, which lowers oxygen levels ROS is used as a signaling molecule for the HIF pathway, which is responsible for the transcription of over 60 genes that code for cell regulation. Over-expressed in cancer cells Parsons, Peter A. "Radiation Hormesis: Challenging Lnt Theory Via Ecological And Evolutionary Considerations." Health Physics 82.4 (2002): Web. 10 Apr
TCA CYCLE
PPP CYCLE Ultimately produces NADPH, which helps prevent oxidative stress.
RESULTS
GOING FORWARD Hormesis argument Learn in greater depth how these processes work Why are people rejecting hormesis? How can IR be beneficial to one’s health?
CITATIONS Doss, H. M. "Ionizing Radiation and Humans â The Basics." Physics Central. APS Physics. Web. 21 Feb Lall, R., S. Ganapathy, M. Yang, S. Xiao, T. Xu, H. Su, M. Shadfan, J. M. Asara, C. S. Ha, I. Ben-Sahra, B. D. Manning, J. B. Little, and Z-M Yuan. "Low-dose Radiation Exposure Induces a HIF-1- mediated Adaptive and Protective Metabolic Response." Cell Death Differ Cell Death and Differentiation 21.5 (2014): Web. 29 Mar Lucas, Jim. "What Is Electromagnetic Radiation?" LiveScience. TechMedia Network, 12 Mar Web. 21 Feb Oka, Yoshiaki. "The Fukushima Daiichi Nuclear Plant Accident Caused by the Massive Tsunami." The Great East Japan Earthquake:Opinion:WASEDA ONLINE. The Japan News. Web. 22 Feb Parsons, Peter A. "Radiation Hormesis: Challenging Lnt Theory Via Ecological And Evolutionary Considerations." Health Physics 82.4 (2002): Web. 10 Apr