Radiation Interactions Direct vs. Indirect May 3, 2012

Radiation Interactions Direct vs. Indirect May 3, 2012

Reminder: email Caitlin millsce@mcmaster.ca your photos Course website: http://www.science.mcmaster.ca/medphys/cour ses/237-medradsc-3u03.html

Radiation is Everywhere

Ionizing Radiation Alpha ( ), beta ( ) Gamma ( ), X-ray Protons, neutrons Ionizing vs. Excitation Ionization Excitation

Particulate Radiation Alpha, beta, protons, neutrons, heavy charged ions, etc. Ionizing Radiation Electromagnetic Radiation (UV), X-rays and Gamma rays

X-ray/γ-ray Absorption Photoelectric effect Low energy range Electron emitted X-ray emitted Compton Scattering High energy range Electron emitted Scattered photon

DNA is Critical Target for Radiation Cell Nucleus - DNA DNA is packaged on chromosomes DNA double helix

Direct vs Indirect Action

Direct vs Indirect Action Particulate radiation = HIGH LET Direct Action Damages DNA directly by breaking bonds Electromagnetic radiation = LOW LET Indirect Action (~two thirds of time) Damages DNA indirectly via radicals and reactive molecules

Indirect Action Most abundant molecule within humans: Water 80% H 2 O H 2 H 2 O + Incoming Radiation H + OH - WATER e - H o HO 2 H 2 O 2 OH o Production of free radicals within the cell can result in indirect effects Can be modified by sensitizers or protectors

http://three.usra.edu/multimedia/radtracks.h tml

DEFINITIONS Absorbed Dose (unit: Gray [Gy]) Energy absorbed per unit mass (J/Kg) Radiation Weighting Factor (WR) Radiation Quality Photons and electrons: 1 Protons: 2 α-particles: 20 Neutrons 1MeV: 20 (most effective neutron) Equivalent Dose (unit: Sievert [Sv]) Equivalent dose = Absorbed dose x W R Eg. If an organ is exposed to 0.15 Gy of 60 Co γ-rays and 0.02 Gy of 1-MeV neutrons Equivalent dose = (0.15 x 1) + (0.02 x 20) = 0.55 Sv

Units Gray and Sieverts (Sv) 1 Sv = 1000 msv 1 msv = 1000 usv 1 mgy = 1 msv (Low LET) msv = millisievert usv = microsievert

Ionizing radiation travels in tracks Free radicals are produced

LINEAR ENERGY TRANSFER (LET) Energy deposited per unit track length usually measured in KeV/um.

DNA Damage

Cellular Radiation Track Distributions Cell Population Radiation Tracks 1 mgy X-Ray Average of 1 track per cell

PET and Brain Activity 4 minute break!!!

Spotlight on Science Dr. MedEvil http://www.youtube.com/watch?v=zfbpjr-wj8w

Microbeam

Charged Particle Microbeam glass capillary 1 m bore 4MV Van de Graaff accelerator 250 m

Microbeams Every cell Single cell Subcellular region Dose Resolution - traversal by a single track Spatial Resolution - resolve the targets Human Stem Cells and Breast Cancer Cells

Biological Microbeam Single Charged Particles (Spot Light on Science Dr. MedEvil U-Tube ) 3 MeV KN (HVE) Van de Graaff accelerator

Subcellular Targeting at Low Doses A B C D Repair Complex Formation - Foci

150 um Cell

DNA Double Strand Breaks Double strand breaks considered most biologically significant lesion Following damage cells can initiate: Repair via HR/NHEJ Apoptosis Cell cycle delays Assortment of repair proteins involved in response to DSBs

53BP1 assay

53BP1 Localizes to sites of DNA damage and produces distinctly visible foci Recently developed an automated assay for detecting and analyzing these foci Ctrl 10mGy 50mGy 100mGy 3Gy

Assay Automation Immunofluorescence to detect DSB foci 53BP1 1 o antibody Alexa 488 fluorescent 2 o antibody All cell work done using the Thermo robotic workstation Individual nuclei and foci identified based on a set of selected values for size, intensity and contrast

Gamma Irradiations Taylor Radiobiology 137 Cs gamma ray source: 662 kev γ - rays Doses: 5 mgy and 10 mgy - 13.5 mgy/min 50 mgy and 100 mgy 50 mgy/min 3 Gy 75 mgy/min

Mammography Irradiations Juravinski Hospital GE Senographe Essential digital mammography scanner: 18 kev X rays Voltage: 29 kvp Current: 63 mas Target/Filter: Rh/Rh Doses: 2 or 10 successive scans (5.2 mgy per scan)

Foci per nucleus Relative Biological Effectiveness 7 y = 0.033x + 4.8074 (X-rays) 6 5 y = 0.0223x + 5.0846 (γ-rays) 4 3 2 1 662 kev γ-rays 29 kvp X-rays 0 0 5 10 15 20 25 30 35 40 45 50 Dose (mgy) 53BP1 foci linear regression (Y = αd + C) α SE R 2 662keV γ-rays 0.0223 0.0090 0.737 29kVp X-rays 0.0330 0.0204 0.724 RBE 1.48 1.09