MRD441 Radiation Biology & Safety PDF

MRD441: RADIATION BIOLOGY & SAFETY  Learning outcomes Upon completion of this lecture, the student should be able to: 1. Understand the radiation damage to DNA. 2. Differentiate between cell survival curves 3. Describe the factors affecting cell survival 4. Describe the acute ra...

MRD441: RADIATION BIOLOGY & SAFETY  Learning outcomes Upon completion of this lecture, the student should be able to: 1. Understand the radiation damage to DNA. 2. Differentiate between cell survival curves 3. Describe the factors affecting cell survival 4. Describe the acute radiation syndrome DNA damage Cell cycle  Cell Cycle and Radiation Injury M phase – mitosis very sensitive to radiation injury G1 phase – resting phase, moderately resistant S phase – DNA synthesis, moderately resistant to radiation G2 resting phase – sensitive G0 non cycling cells – moderate resistance  Cell Cycle and Radiation Injury Mitosis o Chromosomes are condensed DNA is closely packed – bigger target o Repair mechanisms are shut down o Very compressed time scale = 1 hr. o Any DNA injury is fixed in place o Cell may loose large segments of DNA Fragments excluded from nucleus  Cell Cycle and Radiation Injury S phase o Phase of DNA synthesis o Most radiation resistant phase o Cellular repair mechanisms are active Increases repair of radiation damage o Lasts about 5 hours.  Cell Cycle and Radiation Injury G1 o Functional part of cell cycle o Resistance varies with part of phase Goes down as cell nears the G1-S interface Point in cell cycle where apoptosis occurs o Cell death at this point is referred to as interphase death o Longest part of cycle. Lasts hours to years  Cell Cycle and Radiation Injury G2 o Short rest phase before M o Quite radiation sensitive o Short time allows little for injury repair o Radiation injury incurred in S-phase may be repaired May result in a mitotic delay in G2 o Apoptosis-like death may also occur  Cell death Instant death Reproductive death Apoptosis Mitotic death  Instant death Occurs when a volume is irradiated with 1000 Gray of x or gamma ray in a period of seconds or a few minutes The energy absorbed by the cellular components causes DNA breakdown and coagulation of proteins Radiation doses this high do not occur in the diagnostic or therapeutic ranges  Reproductive death Occurs from a dose of 1 – 10 Gray The cell does not die, but becomes sterile Cell looses its capacity to divide The cell will continue to metabolize and synthesize nucleic acids and proteins Transmission of damage to future generations is prevented  Apoptosis Also known as interphase death Cell death before division The dose required to produce interphase death varies  Mitotic death Occurs when the cell dies after one or more divisions Can occur from very small doses Cells that are exposed to radiation during division are most vulnerable to damage Cell Survival Curves  Survival Curve Shoulder Represents the transition zone between single and multiple hit killing The shoulder is representative of the repair capability of the cell population Wider in slowly dividing cells Narrower in rapidly dividing cells Factors affecting survival curve 1. LET 2. Oxygen (Oxygen enhancement ratio) 3. Cell cycle  LET and Effect on Survival LET = Linear Energy Transfer o Measured in keV/micron o Characteristic of particulate radiation High LET radiation increase killing per unit energy deposited. o Results in severe repair deficiencies Effectively removes the repair shoulder  LET and Effect on Survival High LET radiation is densely ionizing Averages >1 ionization event within the span of a DNA molecule. High ionization density increases probability of double strand breaks. Reaches a maximum effect at about 100 keV/micron.  LET and Effect on Survival Photons have an average LET of about 1.