Radiation Mutagenesis & Health Physics
In principle:
Genetic molecules & structures are affected by high-energy ionizing radiation

    ionization may effect  DNA directly or indirectly

Health Physics is the study & control of the effects of radiation on humans.


Primer of Ionizing Radiation
   isotopes have same atomic number (Z) = # protons
                          different atomic mass (A) = Z + N (# protons + # neutrons)
          [nuclides are isotopes differing in energy level: don't confuse with nucleotides]
   radioisotopes (radionuclides) are unstable:
         nucleus & electron shell are energetcially unbalanced
         nucleus undergoes radioactive decay:
              spontaneous release of energy and/or mass as particles or waveforms

Particles
    alpha & beta emitters (32P, 35S, 14C, 3H, 131I)  [read as "P 32" etc.]
        alpha particle: nucleus ejects He nucleus (2 protons + 2 neutrons)
        beta particle: neutron decays to proton + e- (electron)
                           or, proton decays to neutron + e+ (positron)
            [alpha & beta emission may be accompanied by release of gamma photon: 137Cs]

 Waveforms
     gamma emitters (125I)
         radioactive 125I is an isotope of stable (non-radioactive) 127I
           125 = 53 protons + 72 neutrons (versus 127 = 53 Z + 74 N) (see periodic table)
          Decay occurs as electron capture: e- + proton neutron + gamma photon

      Planck's Equation predicts energy content:
           E = h /    where E = energy,   = wavelength, h = Planck's constant
               shorter wavelength radiation more energetic radiation
           Energy: UV (ultraviolet) radiation  <  X-rays  <  gamma rays < cosmic rays

 Neutron activation: N bombardment renders materials radioactive
        "Criticality Incidents" &"Nuclear Excursions"
             Louis Slotin (1910 -1946), Canadian physicist at Los Alamos
             Los Alamos (Dec 1958) & Tokaimura (Sept 1999) accidents
         Enhanced Radiation Weapons:
"Neutron Bombs"

"Fallout"
        fission & fusion weapons introduce radioisotopes into the environment & food chain
            Ex:  Chernobyl accident (April 1986): >1 Ci 137Cs / km2    added dose ~1 mSv / yr

             Fallout products


Genetic effects of ionizing radiation
      direct or indirect radiochemical damage to DNA

      direct effects: formation of thymine dimers  (T~T)
           covalent linkage of adjacent T T bases causes errors in replication
               UV irradiation causes skin cancer
                   photoreactivation or excision repair reverse damage
                   xeroderma pigmentosum is a genetic disease caused by a repair defect

           cross-linking - different DNA molecules covalently joined
                                       H-bonds covalent bonds

           dsDNA chromosome breaks
                 non-homologues join end-to-end to form dicentric chromosomes
                 1920s radium watch dial painters ingested  226Ra [high-energy alpha]

       indirect effects: oxidative damage
            Radiolysis of H20 produces free radicals:
                H2O         H + OH             [hydroxy radical]
                HO + OH H2O2                [hydrogen peroxide]
                H2O2        H  +  HO2-      [superoxide radical]

             oxidation of bases modifies pairing rules
                  8-oxo-7-hydro-deoxyguanosine (GO)
                 dG GO  by oxidation, pairs with   transversion

             Prevention & repair of oxidative damage
                superoxide dismutase (SOD): HO2- + H H2O2
                catalase: H2O2 H2O


Radioisotope exposure & laboratory safety (Health Physics)

Half-life
     physical - Time before 1/2 of radioactivity lost by physical decay (Tp)
     biological - Time before 1/2 of material eliminated from body metabolically (Tb)
     effective - combined physical & biological decay loss ( 1 / Te  =  1/ Tp  +  1/Tb )
            Ex.: Acute Polonium poisoning
 

     body burden - Amount of material that stays in body permanently
           critical organ depends on isotope
           239Pu   - Plutonium: calcium analog, "bone-seeker"
         131,125I   - Radioiodine: used in tests of thyroid function as "thyroid-seeker"
                  3H  - Tritium: enters "body water"
 
Dosimetry of ionizing radiation
     Measures of mass
         curie (Ci) = 1 gm of radium (226Ra)  = 3.7 x 1010 dps
               [dps = disintegration per second = 1 becquerel (Bq)]

     Measures of dose
          How much radiation strikes target?
               Measure this with a Geiger-Muller tube ("Geiger counter")
                     1 Gray (Gy) = 100 Roentgen (R) = 1 J / kg
                           Ex.: typical X-Ray series = 2.2 mGy = 220 mR

          How much radiation is absorbed by body ?
               Depends on radiation type & target
                    1 Gy X-Rays delivers 0.1 rad (radiation-absorbed dose)

           Biological effect depends on nature of radiation
                    1 Gy
X-Rays delivers 1 Sievert (Sv)
                       or,  10mSv = 1 rem [
roentgen-equivalent (in) man - effect dose]

                 Depends on relative biological effect (rbe) of radiation
                     e.g., radionucleotides as nucleic acid labels (32P- & 35S- dNTPs)
                             ingestion direct incorporation into chromosomes  high rbe

                linear energy transfer (LET) = energy / path length
                     How much energy is released during passage through cell / body?
                     gamma & X-rays: (very) high energy over long path length low LET
                     alpha & beta particles: low energy over (very) short path length high LET
                                                                high specific ionization over short path


Consequences of radiation exposure
           Average North American exposed to 1 millisievert (1 mSv) = 0.1 rem / year
                Dose-response curve is linear: no safe threshold
                      Chronic low-level exposure increases incidence of cancer
                US & Canadian NRC sets occupational limits to exposure
                       Exposure threshold for civil population emergency = 10 ~ 50 mSv (Fukushima 2011)

            Acute exposure to 500 mSv produces haematopoetic "radiation sickness"
                     3,000 mSv produces 'gastrointestinal syndrome', fatal without treatment
                     5,000 mSv = LD50/30 : lethal dose for 50% of population in 30 days

Homework: Consider 10 uCi of a gamma- or an alpha-emitter
                                            Which would you rather be exposed to at 1 meter?
                                            Which would you rather swallow?
                                            Explain.


All text material 2014 by Steven M. Carr