Transcript Establishing of calibration curves unstable chromosomal

2010 Student Practice in JINR Fields of Research
Established calibration curve for unstable
chromosomal aberrations induced by
therapeutic protons beam for retrospective
dose estimation
1) Agnieszka Frącka; 2) Ilona Głowacka; 2) Wojciech Wróblewski
1) University of Wrocław; 2) University of Łódź
Supervisors: Marta Deperas- Kaminska and Polina Kutsalo
Laboratory of Radiation Biology, Joint Institute for Nuclear Research
Biological dosimetry – allows to assess an
accidental dose of ionising radiation by analysis
of changes induced in chromosomes of human
peripheral blood lymphocytes
The yield of chromosome aberrations
in peripheral blood lymphocytes is the most sensitive indicator for
past irradiation exposure, therefore it is used in biological
dosimetry for retrospective dose estimation.
References:
• Biological dosimetry: chromosome aberrations analysis for dose assessment. (1986)
International Atomic Energy Agency Technical Report No 260.Vienna.
• Cytogenetic analysis for radiation dose assessment. A manual. (2001) International Atomic
Energy Agency. Vienna.
How are aberrations formed?
ionising radiation
Primary lesions
translocation
dicentric
acentric
fragments
Purpose:
The purpose of our investigation were to establish
calibration curve for unstable aberrations induced by
proton beam routinely use to cancer therapy at
Laboratory of Nuclear Problems at JINR.
What it is calibration curves?
Calibration curves are performed for chromosomal aberrations yields
scored in lymphocytes of several voluntaries exposed in vitro to the
known radiation doses
SCHEME OF THE EXPERIMENT
for the standard metaphase analysis (dicentric assay)
PHA
Culture of
Irradiated
blood
BrdU
colcemid
Fixation
0-24 h
46h
Reference: Cytogenetic analysis for radiation dose assessment.
A manual. (2001) International Atomic Energy Agency. Vienna.
48-50h
light microscope
An example of metaphase stained with Giemsa. Cell carried unstable
aberrations: dicentrics, acentric fragments and centric and acentric rings.
Centric ring
ace
deletion
Acentric ring
Dic
Image visible under light microscope
CABAS is intended for fitting dose-response curves.
The software is intended for fitting a linear-quadratic dose-response relationship by the
maximum-likelihood method. It was designed for the purpose of biological dosimetry based
on the analysis of chromosomal aberrations - dicentrics and rings, scored on Giemsa
stained slides.
Reference: Deperas J. et. al. (2007) CABAS - a freely available PC program for
fitting calibration curves in chromosome aberration dosimeter. Radiat Prot Dosimetry 124:115-123,
2007.
Our results:
140
Number of dic+R per 100 cells
120
Y=A+αD+βD^2
Mean values of aberration frequencies
Fitted curves
Y- aberration yield;
A – control frequency
D – dose [Gy]
α- linear coefficient
β- dose squared coefficient
100
Y=0,0030+0.0980*D+0,0798*D^2
80
60
40
20
0
0.0
0.5
1.0
1.5
2.0
2.5
3.0
Dose [Gy}
Figure 1. Fitted dose response curves for sum of dicentrics and centric rings induced by protons
in chromosomes of 4 donors. Error bars represent the 95% confidence intervals calculated for
the mean values.
Conclusion:
We established dose calibration curve for
unstable chromosomal aberrations
induced by therapeutic proton beam in the
dose range from 0 to 3 Gy.
The calibration curve may be useful to
retrospective dose estimation in case of
accidental exposure to protons.
Acknowledgements
Special thanks to:
• Marta Deperas-Kaminska and Polina
Kutsalo.
• Ewa and Władysław Chmielowscy
• Roman Zawodny
• Stanislav Zdislavovich Pakuliak
X-ray photo - 1896
Thanks for your attention