Dose-response parameters and microdosimetric quantity [1]

Charged particles and microdose

Biologically important dose is given by charged particle (also Compton or photo electrons in the case of photons, and recoil protons or other charged particles in the case of neutrons). When the average dose incident to the cell nucleus is decreased, the dose to the cell nucleus does not proportionally decrease at low doses, where the dose to the hit nucleus is defined only by the quality of the charged particle (LET), and hence only the number of the hit cell nuclei decreases. This minimum dose given by traversal of single charged particle is called “elementary dose” or microdose”. The followings are example of dose calculation for a charged particle (5 MeV alpha particle with LET=132.24 keV/μm passing through a lymphocyte nucleus with 5 μm diameter.

   

Electrons and beta-particles
Electrons and β-particles
Radiation Mean energy Mean LET (keV/μm) Authors Dose range Data Linear term (×10-4/cell/cGy) Quadratic term (×10-6/cell/cGy2) Microdose σ=Dics/cell/path
(MeV) LT LT(cutoff) LD LD(cutoff) (cGy) points α ± (S.E.) β ± (S.E.) (cGy) σ±SE
Electrons(100rad/min) 15 0.214 0.106 0.222 0.117 Purrott et al. 1977 44-511 6 0.400 ± 1.094 6.537 ± 0.425 0.17 6.800E-06 ± 1.860E-05
Electrons(pulsed) 15 0.214 0.106 0.222 0.117 Purrott et al. 1977 53-392.2 7 0.200 ± 1.835 8.093 ± 1.141 0.17 3.400E-06 ± 3.120E-05
Electrons 3 0.204 0.113 0.233 0.135 Bauchinger et al. 1974 128-432** 9 1.000 ± 2.395 3.488 ± 0.485 0.17 1.700E-05 ± 4.072E-05
90Sr-90Y beta 0.6013 0.580 0.126 0.484 0.126 Vulpis et al. 1986 13.8-276 7 8.490 ± 1.566 8.698 ± 0.722 0.22 1.868E-04 ± 3.445E-05
90Y beta 2.281 0.413 Schmid et al. 2006 0-217.6 7 2.290 ± 0.280 0 ± 0 0.34 7.786E-05 ± 9.520E-06
3H beta (80% water) 0.0057 5.594 2.977 6.717 3.025 Vulpis 1984 25-420 8 12.935 ± 1.634 5.731 ± 0.611 4.56 5.898E-03 ± 7.451E-04
3H beta (82% water) 0.0057 5.594 2.977 6.717 3.025 Prosser et al. 1983 10.2-304.5 10 5.652 ± 0.403 1.929 ± 0.172 4.56 2.577E-03 ± 1.838E-04
3H beta (70% water) 0.0057 5.594 2.977 6.717 3.025 Tanaka et al. 1994 0-210 6 20.639 ± 2.539 8.544 ± 1.504 4.56 9.411E-03 ± 1.158E-03
3H beta (80% water)* 0.0057 5.594 2.977 6.717 3.025 Bocian et al. 1977 0-255 5 8.492 ± 1.048 9.353 ± 0.851 4.56 3.872E-03 ± 4.779E-04
*) Including centric rings.
**) Because there are no low-dose points, the data were fitted to Y=C+αD+βD2

References
     Bauchinger, M., Schmid, E. and Rimpl, G. (1974): Interaction distance of primary lesions in the formation of dicentric chromosomes after irradiation of human lymphocytes with 3-MeV electrons in vitro. Mutation Res., 25:83-87.
     Bocian, E., Ziemba-Zak, B., Rosiek, O. and Sablinski, J. (1977): Chromosome aberrations in human lymphocytes exposed to tritiated water in vitro. Top. Radiat. Res. Quat., 12:168-181.
     Prosser, J. S., Lloyd, D. C., Edwards, A. A. and Stather, J. W. (1983): The induction of chromosome aberrations in human lymphocytes by exposure to tritiated water in vitro. Radiat. Prot. Dosimet., 4:21-26.
     Purrott, R. J., Reder, E. J. and Lovell, S. (1977): Chromosome aberration yields induced in human lymphocytes by 15 MeV electrons given at a conventional dose-rate and in microsecond pulses. Int. J. Radiat. Biol., 31: 251-256.
     Schmid, E., Rimpl, G. and Bauchinger, M. (1974): Dose-response relation of chromosome aberrations in human lymphocytes after in vitro irradiation with 3-MeV electrons. Radiat. Res., 57:228-238.
     Tanaka, K., Sawada, S. and Kamada, N. (1994): Relative biological effectiveness and dose rate effect of tritiated water on chromosomes in human lymphocytes and bone marrow cells. Mutation Res., 323:53-61.
     Vulpis, N. (1984): The induction of chromosome aberrations in human lymphocytes by in vitro irradiation with β particles from tritiated water. Radiat. Res., 97:511-518.
     Vulpis, N. and Scarpa, G. (1986): Induction of chromosome aberrations by 90Sr β-particles in cultured human lymphocytes. Mutation Res., 163:277-283.


Protons
Protons
Radiation Energy Mean LET Authors Dose range Data Linear term (×10-4/cell/cGy) Quadratic term (×10-6/cell/cGy2) Microdose σ=Dics/cell/path.
(MeV) LT (keV/μm) (cGy) points α ± (S.E.) β ± (S.E.) ε (cGy) σ±SE
Protons 8.7 5.17 Edwards et al. 1986 6.2-279 9 6.838 ± 0.777 4.362 ± 0.342 4.22 2.886E-03 ± 3.279E-04
Protons 40 1.47 Sasaki 2009 0-300 4 1.086 ± 1.621 4.362 ± 0.700 1.20 1.303E-04 ± 1.945E-04
Protons 60 1.07 Manti et al. 2005 0-500 6 0.660 ± 0.360 1.480 ± 0.090 0.87 5.742E-05 ± 3.132E-05
Protons 4.9 7.9 Takatsuji et al. 1983 16-310 12 28.018 ± 11.021 14.568 ± 5.688 6.45 1.807E-02 ± 7.109E-03
Protons 22.6 4.21 Joksic et al. 2000 0-300 5 18.150 ± 2.040 0.705 ± 0.729 3.43 6.225E-03 ± 6.997E-04
Protons 50 1.23 Todorov 1972, 1975 0-250 5 0.877 ± 1.466 4.698 ± 0.712 1.00 8.770E-05 ± 1.466E-04
Protons 16.5 2.14 Schmid et al. (D1) 1997,Ld=3.5 0-132 6 4.580 ± 0.271 1.805 ± 0.239 1.75 8.015E-04 ± 4.743E-05
Protons 16.5 3.15 Schmid et al. (D2) 1997, Ld=5.3 0-198 6 6.500 ± 1.000 1.400 ± 0.300 2.57 1.671E-03 ± 2.570E-04
Protons 16.5 11.3 Schmid et al. (D3) 1997, Ld=19 0-145 6 32.300 ± 1.300 0 ± 0 9.22 2.978E-02 ± 1.199E-03
Protons 16.5 1.8 Rimpl et al. 1990, Ld=3 14-287 8 4.400 ± 0.700 1.950 ± 0.300 1.47 6.468E-04 ± 1.029E-04
Protons 31 1.83 Bettega et al. 1981 0-200 5 6.260 ± 0.484 1.815 ± 0.286 1.49 9.327E-04 ± 7.212E-05
Protons 12 3.99 Bettega et al. 1981 0-200 5 9.189 ± 1.395 3.501 ± 0.835 3.26 2.996E-03 ± 4.548E-04
Protons 8 5.82 Bettega et al. 1981 0-200 5 24.950 ± 5.770 2.797 ± 3.582 4.75 1.185E-02 ± 2.741E-03
Protons 70 1 Matsubara et al. 1990 (5mm) 10-300 6 2.195 ± 1.842 4.659 ± 0.550 0.82 1.800E-04 ± 1.510E-04
Protons 70 1.15 Matsubara et al. 1990(15mm) 10-300 6 7.508 ± 2.184 4.073 ± 0.927 0.94 7.058E-04 ± 2.053E-04
Protons 70 1.42 Matsubara et al. 1990 (25mm) 10-300 6 9.602 ± 0.691 4.110 ± 0.267 1.16 1.114E-03 ± 8.016E-05
Protons 1000 0.31 Repina et al. 2007 5-200 1.200 ± 0.200 0 ± 0 0.25 3.000E-05 ± 5.000E-06
Protons 7.4 5.84 Bocian 1973 (Lloyd and Edwards 1983) 50-400 15.100 ± 5.640 0.530 ± 0 4.76 7.188E-03 ± 2.685E-03
Protons 0.88 28 Mognato et al. 2003 0-200 6 61.800 ± 8.900 0 ± 0 22.84 1.412E-01 ± 2.033E-02

References
     Bettega, D., Dubini, S., Conti, A. M. F, Pelucchi, T. and Lombardi, L. T. (1981): Chromosome aberrations induced by protons up to 31 MeV in cultured human cells. Radiat. Environ. Biophys., 19: 91-100.
     Edwards, A. A., Lloyd, D. C., Prosser, J. S., Finnon, P. and Moquest, J. E. (1986): Chromosome aberrations induced in human lymphocytes by 8.7 MeV protons and 23.5 MeV helium-3 ions. Int. J. Radiat. Biol., 50: 137-145.
     Joksie, G., Pajovic, S. B., Stankovic, M., Pejic, S., Kasapovic, J., Guttone, G., Calonghi,N., Masotti, L. and Kanazir, D. T. (2000): Chromosome aberrations, micronuclei, and sctivity of superoxide dismutases in human lymphocytes after irradiation in vitro. Cell. Mol. Life Sci., 57:842-850.
     Matsubara, S., Ohara, H., Hiraoka, T., Koike, S., Ando, K., Yamaguchi, H., Kuwabara, Y., Hoshina, M. and Suzuki, S. (1990): Chromosome aberration frequencies produced by a 70-MeV proton beam. Radiation Research, 123, 182-191.
     Manti, L., Durante, M., Cirrone, G. A., Grossi, G., Lattuada, M., Sabini, M. G., Scampoli,P., Valastro, L. and Gialanella, G. (2005): Modelled microgravity does not modify the yield of chromosome aberrations induced by high-energy protons in human lymphocytes. Int. J. Radiat. Biol., 81:147-155.
     Mognato, M., Bortoletto, E., Ferraro, P., Baggio, L., Cherubini, R., Canova, S., Russo, A. and Celotti, L. (2003): Genetic ddamage induced by in vitro irradiation of human G0 lymphocytes with low-energy protons (23 keV/microm): HPRT mutations and chromosomeaberrations. Radiat. Res., 160:52-60.
     Repina, L. A., Abrosimova, A. N., Timoshenko, G. N. and Issinskii, I. B. (2007): Cytogenetic effects in human lymphocytes in vitro after irradiation by protons with 1-GeV energy. Aviakosm. Ekolog. Med., 41:29-32 (Russian).
     Rimple, G. R., Schmid, E., Braselmann, H. and Bauchinger, M. (1990): Chromosome aberrations induced in human lymphocytes by 16.5 MeV protons. International Journal of Radiation Biology, 58, 999-1007.
     Sasaki, M. S. (2009): Advances in the biophysical and molecular basis of radiation cytogenetics. Int. J. Radiat. Biol., 85:26-47.
     Schmid, E., Roos, H., Rimple, G. and Bauchinger, M. (1997): Chromosome aberration frequencies in human lymphocytes irradiated in a multi-layer array by protons with different LET. International Journal of Radiation Biology, 72, 661-665.
     Takatsuji, T., Takekoshi, H. and Sasaki, M. S. (1983): Induction of chromosome aberrations by 4.9 MeV protons in human lymphocytes. International Journal of Radiation Biology, 44, 553-562.
     Todorov, S. L., Grigor’ev, Y. G., Rizhov, N. I., Ivanov, B. A., Malyutina, T. S. and Mileva, M. S. (1972) Dose-response relationship for chromosome aberrations induced by X-rays or 50 MeV protons in human peripheral lymphocytes. Mutation Research, 15, 215-220.


Alpha-particles
Alpha-particles
Radiation Mean Mean LET Authors Dose range Data Linear term (×10-4/cell/cGy) Quadratic term (×10-6/cell/cGy2) Microdose σ=Dics/cell/path.
energy (MeV) LT (keV/μm) (cGy) points α ± (S.E.) β ± (S.E.) (cGy) σ ± SE
23 MeV α 23 28.03 Takatsuji et al. 1984 25.6-299 7 74.180 ± 6.190 2.234 ± 5.544 22.87 1.696E-01 ± 1.416E-02
18 MeV α 18 34.01 Sasaki et al. 1998 27-270 5 70.230 ± 6.510 4.853 ± 2.913 27.75 1.949E-01 ± 1.807E-02
8.4 MeV α 8.4 61.8 Sasaki et al. 1998 30-150 4 96.390 ± 10.570 4.183 ± 7.379 50.42 4.860E-01 ± 5.329E-02
3.85 MeV α 3.85 109 Durante et al. 1995 0-200 7 44.080 ± 7.920 0 ± 4.088 88.93 3.920E-01 ± 7.043E-02
Helium-3 23.5 21 Edwards et al. 1986 4.7-282 8 40.500 ± 3.200 0 ± 1.800 17.13 6.938E-02 ± 5.482E-03
241Am α 5.49 125.9 DuFrain et al. 1979* 0.85-6.84 8 95.135 ± 4.170 0 ± 0 102.72 9.772E-01 ± 4.283E-02
241Am α 2.7 169.5 Schmid and Roos 2009 27.700 ± 2.000 0 ± 0 122.38 3.390E-01 ± 2.448E-02
241Am α 2.7 150 Mestres et al. 2004 20-100 4 36.780 ± 3.210 1.689 ± 3.853 122.38 4.501E-01 ± 3.928E-02
241 Am α 2.7 150 Schmid et al. 1996 0-100 9 26.910 ± 2.630 1.639 ± 3.455 122.38 3.293E-01 ± 3.219E-02
241 Am α 2.7 150 Baraquinero et al. 2004 0-100 9 27.510 ± 3.960 1.879 ± 4.661 122.38 3.367E-01 ± 4.846E-02
241 Am α (PCC) 3.45 127.15 Greinert et al. 1999 100-300 3 61.140 ± 1.758 0 ± 0 103.74 6.343E-01 ± 1.824E-02
225Ac/213Bi α 4.95 138.568 Tawn et al. 2007, 2009 0-50 7 33.600 ± 0.470 0 ± 0 113.06 3.799E-01 ± 5.314E-03
238Pu α (3.5) 155 Purrott et al. 1980 6.5-160 6 31.680 ± 2.570 4.696 ± 1.838 126.46 4.006E-01 ± 3.250E-02
239Pu α 3.5 116 Cornforth et al. 2002 0-220 5 55.650 ± 5.590 0 ± 2.859 94.64 5.267E-01 ± 5.290E-02
242Cm α 4.9 140 Edwards et al. 10.6-282 9 28.410 ± 3.810 0 ± 1.591 114.22 3.245E-01 ± 4.352E-02
*) The dose was re-evaluated by A. A. Edwards to be at least 3 times higher than that described (Edwards, A. A., Int. J. Radiat. Biol., 38:83-91, 1980.
Commentary: When the dose is adjusted by lymphocyte survival (D0=3Gy), the dicentric response could be Y=(30.405±1.332)×10-4/cGy

References
     Barquinero, J. F., Stephan, G. and Schmid, E. (2004): Effect of americium-241 α-particles on the dose-response of chromosome aberrations in human lymphocytes analysed by fluorescence in situ hybridization. Int. J. Radiat. Biol., 80:155-164.
     Cornforth, M. N., Bailey, S. M. and Goodwin, E. H. (2002): Dose responses for chromosome aberrations produced in noncycling primary human fibroblast by alpha particles, and by γ rays delivered at sublimiting low dose rates. Radiat. Res., 158:43-53.
     DuFrain, R. J., Littlefield, L. G., Joiner, E. E. and Frome, E. L. (1979): Human cytogenetic dosimetry: a dose-response relationship for alpha particle radiation from 241Am. Health Phys., 37:279-289.
     Durante, M., Grossi, G. F., Gialanella, G., Pugliese, M., Nappo, M. and Yang, T. C. (1995): Effects of α-particles on survival and chromosomal aberrations in human mammary epithelial cells. Radiat. Environ. Biophys., 34: 195-204.
     Edwards, A. A., Purrott, R. J., Prosser, J. S. and Lloyd, D. C. (1980): The induction of chromosome aberrations in human lymphocytes by alpha-radiation. Int. J. Radiat. Biol., 38:83-91.
     Edwards, A. A., Lloyd, D. C., Prosser, J. S., Finnon, P. and Moquet, J. E. (1986): Chromosome aberrations induced in human lymphocytes by 8.7 MeV and 23.5 MeV herium-3 ions. Int. J. Radiat. Biol., 50:137-145.
     Greinert, R., Thieke, C., Detzier, E., Boguhn, O., Frankenberg, D. and Harder, D. (1999): Chromosome aberrations induced in human lymphocytes by 3.45 MeV α particles analyzed by premature chromosome condensation. Radiat. Res., 152:412-420.
     Mestres, M., Caballin, M. R., Schmid, E., Stephan, G., Sachs, R., Barrios, L. and Barquinero, J. E. (2004): Analysis of α-particle induced chromosome aberrations in human lymphocytes, using pan-centromeric and pan-telomeric probes. Int. J. Radiat. Biol., 80:737-744.
     Purrott, R. J., Edwards, A. A., Lloyd, D. C. and Stather, J. W. (1980): The induction of chromosome aberrations in human lymphocytes by in vitro irradiation with α-particles from plutonium-239. International Journal of Radiation Biology, 38, 277-284.
     Sasaki, M. S., Takatsuji, T. and Ejima, Y. (1998): The F value cannot be ruled out as a chromosomal fingerprint of radiation quality. Radiat. Res., 150:253-258.
     Sasaki, M. S. (2009): Advances in the biophysical and molecular basis of radiation cytogenetics. Int. J. Radiat. Biol., 85:26-47.
     Schmid, E., Hieber, L., Heinzmann, U., Roos, H. and Kellerer, A. M. (1996): Analysis of chromosome aberrations in human peripheral lymphocytes induced by in vitro α-particle irradiation. Radiat. Environ. Biophys., 35: 179-184.
     Schmid, E. and Roos, H. (2009): Influence of the bystander phenomenon on the chromosome aberration pattern in human lymphocytes induced by in vitro α-particle exposure. Radiat. Environ. Biophys., 48:181-187.
     Tawn, E. J. and Thierens, H. (2009): Dose response relationships for chromosome aberrations induced by low doses of alpha-particle radiation. Radiat. Prot. Dosimet., 135:268-271.
     Takatsuji, T. and Sasaki, M. S. (1984): Dose-effect relationship of chromosome aberrations induced by 23 MeV alpha particles in human lymphocytes. Int. J. Radiat. Biol., 45: 237-243.


HZE-ions
Accelerated ions (HZE)
Radiation Mean energy Mean LET Authors Dose range Data Linear term (×10-4/cell/cGy) Quadratic term (×10-6/cell/cGy2) Microdose σ=Dics/cell/path
(MeV) LT (keV/μm) (cGy) points α ± (S.E.) β ± (S.E.) ε (cGy) σ ± SE
Helium-4 20.5 31.4 Di Giorgio et al. 2004 0-302.9 9 37.3 ± 1.8 0 ± 0 25.62 9.556E+02 ± 4.612E+01
Oxygen-16 1480 52 Di Giorgio et al. 2004 0-160 10 56.6 ± 4.5 0 ± 0 42.43 2.402E+03 ± 1.909E+02
Carbon-12 425 61 Di Giorgio et al. 2004 0-147 9 67.4 ± 5.3 0 ± 0 49.77 3.354E+03 ± 2.638E+02
Oxygen-16 996 69 Di Giorgio et al. 2004 0-222 9 38.5 ± 2.9 0 ± 0 56.3 2.168E+03 ± 1.633E+02
Neon-20 212 460 Edwards et al. 1994 0.41 ± 0.015 0 ± 0 375.31 1.539E+02 ± 5.630E+00


References
     Di Giorgio, M., Edwards, A. A., Moquest, J. E., Finnon, P., Hone, P. A., Lloyd, D. C., Kreiner, A. J., Schuff, J. A., Taja, M. R., Vallerga, M. B., López, F. O., Burlón, A., Debray, M. E. and Valda, A. (2004): Chromosome aberrations induced in human lymphocytes by heavy charged particles in track segment mode. Radiat. Protect. Dosimet., 108: 47-53.
     Edwards, A. A., Finnon, P., Moquet, J. E., Lloyd, D. C., Darroudi, F. and Natarajan, A. T. (1994): The effectiveness of high energy neon ions in producing chromosomal aberrations in human lymphocytes. Radiat. Protect. Dosimet., 52:299-203.