Microdosimetric studies of Auger electrons from DNA-incorporated 123-I using the micronucleus assay and the Geant4 Monte Carlo simulation tookit

Fourie, Hein (2014-12)

Thesis (MSc)--Stellenbosch University, 2014.


ENGLISH ABSTRACT: This study’s focus is on the determination and quantization of radiation damage on a cellular level due to the decay of the Auger electron-emitting 123I and the replication of this energy deposition using Geant4 Monte Carlo simulations. The relatively short half-life of 123I (13.2 hours) makes it ideal for studies of Auger electrons which induce biological damage similar to that of high linear energy transfer radiations, when permitted to deposit their energy in close proximity to DNA. Due to small cellular dimensions, direct dose measurements are impossible but estimates may be made from Monte Carlo simulations. In this investigation the thymidine analogue 5-[123I]-iodo-2-deoxyuridine (123IUdR) was used to incorporate the 123I into the cellular DNA of T-lymphocytes from two human donors. Radiation induced micronuclei were numerated in binucleated cells using fluorescence microscopy. The energy deposition per decay of 123I was calculated within a spherical geometry, having the same size and density as a human lymphocyte, using the open source Geant4 toolkit. The absorbed energy per disintegration was used to convert the incorporated 123I activity (Bq) into absorbed dose (Gy) values, in order to compare the biological damage caused by the radioactive iodine to 60Co γ-radiation. A linear relationship between micronuclei frequency and 123I activity could be established. The linear dose-response noted for Auger electrons in the study is indicative of the high-LET nature of these particles. Using the linear-quadratic dose-response curve for micronuclei frequencies following exposure to graded doses of 60Co γ-rays, the relative biological effectiveness (RBE) of the DNA incorporated 123I estimated in this work was found to range from 19 ± 10 to 32 ± 7 for lymphocyte donor 1 and 15 ± 6 to 42 ± 11 for donor 2. The dose limiting RBE (RBEM) for lymphocyte donor 1 and 2 are respectively 34 ± 8 and 50 ± 15 and follows the expected shift in terms of the inherent radiosensitivity of the donors. We also considered the inclusion of the S-phase fraction of the lymphocytes in the dosimetry calculations. The resultant RBEs of the dose points of lymphocyte donor 1 ranges from 4 ± 2 to 7 ± 2, and those of donor 2 ranges from 3 ± 1 to 9 ± 2. The RBEM for lymphocyte donor 1 and 2 are respectively 7 ± 2 and 11 ± 3. The inclusion of the S-phase fraction reduces the calculated RBEs significantly and these observed RBE values relate well to those obtained in studies with fibroblasts and 125IUdR.

AFRIKAANSE OPSOMMING: Hierdie studie fokus op die bepaling en kwantisering van stralingskade op 'n sellulêre vlak as gevolg van die verval van 123I wat Auger elektrone afgee, asook die simulering van hierdie energie afsetting met behulp van die Geant4 Monte Carlo program. Die relatiewe kort half-leeftyd van 123I (13.2 uur) maak dit ideaal vir studies van Auger elektrone wat biologiese skade soortgelyk aan dié van 'n hoë lineêre-energie-oordrag uitstraling veroorsaak, indien die energie van die elektrone naby sellulêre DNA geabsorbeer word. As gevolg van die klein sellulêre dimensies is direkte dosis metings egter onmoontlik, maar skattings kan gemaak word met behulp van Monte Carlo simulasies. Die timidien analoog 5-[123I]-jodo-2-deoxyuridien (123IUdR) was in hierdie ondersoek gebruik om die 123I in die DNA van menslike T-limfosiete in te bou. Mikrokerne in dubbel-kernige selle wat vorm as gevolg van die Auger elektrone was getel met behulp van fluoressensie mikroskopie. Die energie afsetting per 123I verval was bereken binne ‘n sferiese geometrie, met dieselfde grootte en digtheid as 'n menslike limfosiet, met behulp van die Geant4 sagteware. Die geabsorbeerde energie per verval was gebruik om die geïnkorporeerde 123I aktiwiteit (Bq) om te skakel na ‘n waarde van geabsorbeerde dosis (Gy), ten einde die biologiese skade wat veroorsaak word deur die radioaktiewe jodium-123 met kobalt-60 gamma straling te vergelyk. ‘n Lineêre verwantskap tussen die mikrokerne frekwensies en die 123I aktiwiteit is vasgestel. Hierdie verwantskap vir Auger elektrone is 'n aanduiding van die hoë lineêre-energie-oordrag van hierdie deeltjies. Die lineêr-kwadratiese dosis-effek krommes vir mikrokerne frekwensies na blootstelling aan 60Co γ-strale was gebruik om die relatiewe biologiese doeltreffendheid (RBE) van die DNA geïnkorporeerde 123I te beraam. RBE waardes wissel van 19 ± 10 tot 32 ± 7 vir limfosiete van skenker 1 en 15 ± 6 tot 42 ± 11 vir skenker 2. Die dosis beperkte RBE (RBEM) vir limfosiet skenker 1 en 2 is onderskeidelik 34 ± 8 en 50 ± 15 en volg die verwagte skuif in terme van die inherente radiogevoeligheid van die skenkers. Die fraksie van limfosiete wat in S-fase was tydens die blootstelling aan 125IUdR was ingesluit in verdere dosimetrie berekeninge. Die gevolglike RBEs van die dosispunte van limfosiete van skenker 1 wissel van 4 ± 2 tot 7 ± 2 en dié van skenker 2 wissel van 3 ± 1 tot 9 ± 2. Die RBEM vir limfosiet skenker 1 en 2 is onderskeidelik 7 ± 2 en 11 ± 3. Die insluiting van die S-fase fraksie verminder die berekende RBEs aansienlik en die RBE waardes waargeneem hou goed verband met die wat in studies met fibroblaste en 125IUdR verkry is.

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