Radiation Mutagenesis & Health Physics
In principle:
Radiation affects genetic systems by high-energy ionization of molecules;

    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]

 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
            short wave length radiation more energetic radiation
           Energy: UV (ultraviolet) radiation  <  X-rays  <  Gamma Rays < Cosmic Rays

 Neutron activation: exposure of materials to neutron bombardment
       contamination versus activation
       "Neutron bombs" & "Nuclear Excursions":
             Los Alamos accident (December 1958)
             Tokaimura accident (Sept 1999)

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




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 bases: causes errors in replication
           UV irradiation can cause skin cancer
               photoreactivation or excision repair reverse damage
               xeroderma pigmentosum is a genetic disease caused by a repair defect

       indirect effects: Oxidative damage -
            Radiolysis of H20 produces free radicals:
                H2O H + OH               [hydroxy radical]
                HO + OH  H2O2          [hydrogen peroxide]
                HOOH  H  +  HO2-      [superoxide radical]
           oxidation of bases modifies pairing rules
                  8-oxo-7-hydro-deoxyguanosine (GO)
                 dG  GO  by oxidation, pairs with   transversion
           single-strand  chromosome breaks - broken ends peroxidized
           double-strand  chromosome breaks -
                 non-homologues join end-to-end to form dicentric chromosomes
                226Ra -  radium watch dial painters
          cross-linking - different DNA molecules covalently joined
                                    H-bonds converted to covalent bonds

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


Radioisotope exposure & laboratory safety (Health Physics)

Half-life
     physical - Time before 1/2 of radioactivity lost by physical decay
     biological - Time before 1/2 of material eliminated from body metabolically
     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
                         
or, 1 R = 10 mGy
                           Ex.: typical chest X-Ray = 1 mGy = 100 mR

          How much radiation is absorbed by body ?
               Depends on target (e.g., skin versus gonads)
                    [1 Gy delivers 0.1 rad (radiation-absorbed dose)
                      or, 1 rad = 10 mGy]

        roentgen-equivalent (in) man (rem) - effect dose
               What is biological effect of 1 R (10 mGy) ? 
                   
[1 Gy delivers 1 Sievert (Sv)
                       or,  1 rem = 10mSv

Consequences of radiation exposure
           Average person is exposed to 1 millisievert (1 mSv) = 0.1 rem / year
                Acute exposure to 500 mSv produces "radiation sickness"
                5,000 mSv = LD50/30 : lethal dose for 50% of population in 30 days
                 Chronic low-level exposure increases incidence of cancer

           Dose-response curve is linear: no safe threshhold
               Depends on relative biological effect (rbe) of radiation
                     e.g., radionucleotides in nucleic acid experiments (32P- & 35S- dNTPs)
                             direct incorporation into chromosomes  high rbe
                Related to 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


All text material © 2007 by Steven M. Carr