Page 301 - 2014 Printable Abstract Book
P. 301
computational model is calibrated using the relative frequencies and distributions of chromosomal
aberrations reported in the literature. The model considers fractionated deposition of energy to
approximate dose rates of the space flight environment. The joined model also predicts of the yields and
sizes of translocations, dicentrics, rings, and more complex-type aberrations formed in the G0/G1 cell
cycle phase during the first cell division after irradiation. We found that the main advantage of the joined
model is our ability to simulate small doses: 0.05-0.5 Gy. At such low doses, the stochastic track structure
proved to be indispensable, as the action of individual delta-rays becomes more important.
(PS5-25) Microdosimetry-based clustering model of DNA repair domains predicts relative biological
1
2
1
effectiveness for cell survival. Sylvain Costes ; Nikhil Vadhavkar ; Walter Georgescu ; Thomas
1
1
Deschamps ; and Jonathan Tang , Life Sciences Division, Lawrence Berkeley National Laboratory,
1
Berkeley, CA and MIT 3D Optical Systems Lab, Harvard-MIT Health Sciences and Technology, Cambridge,
MA
2
The linear-quadratic model has been used for decades to interpret cell survival after exposure to
ionizing radiation. These models are known to be inadequate when energy is deposited in a concentrated
manner in the cell. The reason for this inability to predict cell survival under various energy deposition
scenarios is the lack of a biological mechanism. Most cell survival models have hypothesized that DNA
double strand breaks (DSBs) are the events responsible for cell death and that DSBs are typically isolated
and repaired at the site of damage. In contrast, our previous work leads us to hypothesize that DSBs are
first moved into repair domains before they are being processed. This leads to non-linear response at
higher doses with multiple DSBs being processed simultaneously in common repair domains, increasing
chances of mis-repair, chromosomal rearrangement and cell death. Previous experimental work
characterizing the dose dependence of Radiation-induced foci (RIF) in human breast epithelial cells
(HMEC) is used here to validate a DSB clustering model on X-ray data. Probability of inducing cell death
from isolated DSB and clustered DSB can be inferred via computer simulations leading to the best fit of
survival curves of HMEC exposed to X-ray. The clustering mechanisms that showed the best fits for both
DNA damage and cell death suggest the nucleus is made of an array of regularly spaced repair domains.
This model was then tested to predict the dose response of RIF and cell death after exposure to densely
ionizing particles instead of X-ray. Predictions were extremely accurate. With such an approach,
parameters derived experimentally on X-ray are now sufficient to predict for the first time the relative
biological effectiveness of high-LET radiation by simply including microdosimetric properties of ion tracks.
This approach opens the door to a unified model to predict risk to cosmic rays for astronauts or to optimize
treatment planning for hadron-therapy or hypofractionated radiotherapy.
(PS5-26) Stimulation of triple negative breast cancer cells migration in pre-irradiated mammary gland.
1
1
2
1
1
Gina Bouchard ; Hélène Therriault ; Yves Bérubé-Lauzière ; Rachel Bujold ; Caroline Saucier ; and Benoit
1
1
Paquette , Université de Sherbrooke, Sherbrooke, Canada and Centre Hospitalier Université de
Sherbrooke, Sherbrooke, Canada
2
Triple negative breast cancer (TNBC, estrogen receptor, progesterone receptor and HER2/neu
negative) is in the spotlight of oncologists and researchers since it is usually referring to high grade and
poor prognostic of breast cancer. Conventional therapy appears to be inefficient according to low
299 | P a g e
aberrations reported in the literature. The model considers fractionated deposition of energy to
approximate dose rates of the space flight environment. The joined model also predicts of the yields and
sizes of translocations, dicentrics, rings, and more complex-type aberrations formed in the G0/G1 cell
cycle phase during the first cell division after irradiation. We found that the main advantage of the joined
model is our ability to simulate small doses: 0.05-0.5 Gy. At such low doses, the stochastic track structure
proved to be indispensable, as the action of individual delta-rays becomes more important.
(PS5-25) Microdosimetry-based clustering model of DNA repair domains predicts relative biological
1
2
1
effectiveness for cell survival. Sylvain Costes ; Nikhil Vadhavkar ; Walter Georgescu ; Thomas
1
1
Deschamps ; and Jonathan Tang , Life Sciences Division, Lawrence Berkeley National Laboratory,
1
Berkeley, CA and MIT 3D Optical Systems Lab, Harvard-MIT Health Sciences and Technology, Cambridge,
MA
2
The linear-quadratic model has been used for decades to interpret cell survival after exposure to
ionizing radiation. These models are known to be inadequate when energy is deposited in a concentrated
manner in the cell. The reason for this inability to predict cell survival under various energy deposition
scenarios is the lack of a biological mechanism. Most cell survival models have hypothesized that DNA
double strand breaks (DSBs) are the events responsible for cell death and that DSBs are typically isolated
and repaired at the site of damage. In contrast, our previous work leads us to hypothesize that DSBs are
first moved into repair domains before they are being processed. This leads to non-linear response at
higher doses with multiple DSBs being processed simultaneously in common repair domains, increasing
chances of mis-repair, chromosomal rearrangement and cell death. Previous experimental work
characterizing the dose dependence of Radiation-induced foci (RIF) in human breast epithelial cells
(HMEC) is used here to validate a DSB clustering model on X-ray data. Probability of inducing cell death
from isolated DSB and clustered DSB can be inferred via computer simulations leading to the best fit of
survival curves of HMEC exposed to X-ray. The clustering mechanisms that showed the best fits for both
DNA damage and cell death suggest the nucleus is made of an array of regularly spaced repair domains.
This model was then tested to predict the dose response of RIF and cell death after exposure to densely
ionizing particles instead of X-ray. Predictions were extremely accurate. With such an approach,
parameters derived experimentally on X-ray are now sufficient to predict for the first time the relative
biological effectiveness of high-LET radiation by simply including microdosimetric properties of ion tracks.
This approach opens the door to a unified model to predict risk to cosmic rays for astronauts or to optimize
treatment planning for hadron-therapy or hypofractionated radiotherapy.
(PS5-26) Stimulation of triple negative breast cancer cells migration in pre-irradiated mammary gland.
1
1
2
1
1
Gina Bouchard ; Hélène Therriault ; Yves Bérubé-Lauzière ; Rachel Bujold ; Caroline Saucier ; and Benoit
1
1
Paquette , Université de Sherbrooke, Sherbrooke, Canada and Centre Hospitalier Université de
Sherbrooke, Sherbrooke, Canada
2
Triple negative breast cancer (TNBC, estrogen receptor, progesterone receptor and HER2/neu
negative) is in the spotlight of oncologists and researchers since it is usually referring to high grade and
poor prognostic of breast cancer. Conventional therapy appears to be inefficient according to low
299 | P a g e
