Thesis (MScMedSc)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: Background: The assignment of radiation weighting factors to high energy neutron
sources is important as there is reason to believe that neutron relative biological
effectiveness (RBE) may be related to the inherent radiosensitivity of different
individuals. A study was undertaken to quantify the inherent radiosensitivities of
lymphocytes obtained from different donors to 60Co y-rays and p(66)/Be neutrons.
For this a novel semi-automated image analysis process has been employed. In
addition the responses of lymphocytes with different inherent radiosensitivities have
also been tested using Auger electrons emitted by 123I.
Methods: The RBE of neutrons was determined from dose-response curves for
lymphocytes from different donors. Isolated T-lymphocytes irradiated in vitro were
cultured to induce micronuclei in binucleated cells and micronuclei (MN) formations
numerated using a semi-automated Metafer microscope system. The accuracy in
obtaining dose response curves with this method has been tested by evaluating
dispersion parameters of MN formations in the response to the different treatment
modalities. Differences in the inherent radiosensitivities of cells from different donors
were ascertained using 95 % confidence ellipses. [123I]Iododeoxyuridine was
prepared in a formulation that allows incorporation of 123I into the DNA of
lymphocytes. Micronucleus formations to this treatment were evaluated in
lymphocytes with established differences in inherent radiosensitivities. Results: The image analysis system proved to be consistent in detecting micronuclei
frequencies in binucleated lymphocytes. As a result, differences in the inherent
radiosensitivities of different individuals were distinctive and could be stated at the
95% confidence level. The inter-individual radiosensitivity variations were
considerably smaller for blood cells exposed to high energy neutrons compared to
60Co y-rays. Relative biological effectiveness (RBEM) values between 2 and 13 were determined that are highly correlated with the inherent radioresistance of
lymphocytes obtained from different individuals. As such radiation weighting factors
for high energy neutrons cannot be based on cytogenetic damage determined in
lymphocytes from a single donor. Dispersion parameters for micronuclei formations proved to vary according to ionization density. The variation in RBE with neutron
dose changed according to theoretical considerations and automated image analysis
detection of MN is thus a suitable method to quantify radiation weighting factors.
A clear reduction in the variation in radiosensitivity is noted for lymphocytes exposed
to Auger electrons compared to 60Co y-rays. The effectiveness of Auger electrons
from [123I]IUdR to induce biological damage is demonstrated as the number of disintegrations needed to yield micronuclei formations was found to be more than
two orders of magnitude less than that of other compounds. An increase in the RBE
of Auger electrons with radioresistance can be inferred from these findings and
constitutes a basis for therapeutic gain in treating cells compared to using
radioisotopes emitting low-LET radiation. / AFRIKAANSE OPSOMMING: Agtergrond: Die bepaling van straling gewigsfaktore vir hoë energie neutron bronne
is belangrik, aangesien daar rede is om te glo dat die relatiewe biologiese
effektiwiteit (RBE) kan verband hou met die inherente stralings sensitiwiteit van
verskillende individue. Hierdie studie is onderneem om die inherente
radiosensitiwiteit van limfosiete verkry vanaf verskillende skenkers te kwantifiseer na
blootstelling aan 60Co y -strale en p(66)/Be neutrone. Vir hierdie doel is daar van 'n
semi-outomatiese beeldontleding metode gebruik gemaak. Daarbenewens is die
reaksie van limfosiete met vooraf bepaalde inherente radiosensitiwiteite ook getoets
aan die hand van Auger elektrone wat uitgestraal word deur 123I.
Metodiek: Die RBE van neutrone was bepaal uit dosis mikrokerne frekwensie
verwantskappe verkry vir limfosiete. Geïsoleerde T-limfosiete was in vitro bestraal en
gekweek om mikrokerne te vorm in dubbelkernige selle. Die mikrokerne was
gekwantifiseer deur die gebruik van 'n semi-outomatiese Metafer mikroskoop stelsel.
Die akkuraatheid in die verkryging van dosis-effek krommes met hierdie metode is
getoets deur die ontleding van verspreidings parameters van MN vorming in reaksie
op behandeling met die verskillende stralings modaliteite. Verskille in die inherente
stralingsensitiwiteite van die selle van verskillende skenkers was vasgestel deur die
konstruksie van 95 % betroubaarheidsinterval ellipse. [123I]Iododeoxyuridine was ook
berei om 123I in die DNA van limfosiete in te bou. Die mikrokerne vorming op die
behandeling is beoordeel in limfosiete met gevestigde verskille in inherent
radiosensitiwiteite. Resultate: Die beeld analise stelsel bewys om konsekwent te wees in die opsporing
van mikrokerne wat vorm in dubbelkernige limfosiete. Verskille in die inherente
radiosensitiwiteite van verskillende skenkers kon vasgestel word op die 95 %
betroubaarheidsvlak. Die skommeling in inter-individuele stralings sensitiwiteite was
kleiner vir bloed selle blootgestel aan hoë-energie neutrone in vergelyking met 60Co
y-strale. Relatiewe biologiese effektiwiteit (RBEM) waardes tussen 2 en 13 is bepaal
wat sterk verband hou met die inherente radioweerstandbiedendheid van limfosiete
verkry vanaf verskillende persone. As sodanig kan straling gewigsfaktore vir hoë energie neutrone nie gebaseer word op sitogenetiese skade in limfosiete van 'n
enkele skenker nie. Verspreidings parameters vir mikrokern vorming het gewissel as
‘n funksie van ionisasiedigtheid van die straling. Die verandering in RBE met neutron
dosis verloop volgens teoretiese oorwegings en die semi-outomatiese
beeldontledings metode om mikrokerne op te spoor is dus geskik om stralings
gewigsfaktore te kwantifiseer.
'n Duidelike afname in die verandering in die stralingsensitiwiteite is waargeneem vir
limfosiete blootgestel aan Auger elektrone in vergelyking met 60Co y-strale. Die hoë
doeltreffendheid van Auger elektrone afkomstig van [123I]IUdR om biologiese skade
te veroorsaak, word weerspieël deur die feit dat die getal disintegrasies wat nodig is
om mikrokerne te vorm meer as twee ordes grootte minder is as dié van ander
verbindings. 'n Toename in die RBE van Auger elektrone in selle wat
radioweerstandbiedend is kan afgelei word uit hierdie bevindinge. Dit vorm 'n basis
vir terapeutiese wins in die behandeling van selle in vergelyking met die gebruik van
radio-isotope wat lae ionisasie digthede tot stand bring.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/71921 |
| Date | 12 1900 |
| Creators | Beukes, Philip Rudolph |
| Contributors | Slabbert, Jacobus, Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medical Imaging and Clinical Oncology. |
| Publisher | Stellenbosch : Stellenbosch University |
| Source Sets | South African National ETD Portal |
| Detected Language | Unknown |
| Type | Thesis |
| Format | 89 p. : col. ill. |
| Rights | Stellenbosch University |
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