Page 274 - 2014 Printable Abstract Book
P. 274
with rodent models. We utilized cells derived from spontaneously occurring canine tumors to study dose-
dependent survival of tumor cells exposed to ionizing radiation and subsequent hypoxia of varying
severity and duration with the goal of improving scientific understanding of cellular and physiological
responses to single fraction, high dose irradiations such as those occurring during SRT.
(PS4-67) Defining the role of the tumor microenvironment and DNA repair in cell survival responses
1
following exposure to intensity-modulated radiation fields. Karl T. Butterworth, PhD ; Stephen J.
1;2
2
2
1
McMahon, PhD ; Conor K. McGarry, PhD ; Aidan J. Cole, MD ; Suneil Jain, M.B., B.Ch ; Joe M. O'Sullivan,
1
1;2
3;2
FRR(RCSI) ; Alan R. Hounsell, Phd ; and Kevin M. Prise, PhD, Queen's University Belfast, Belfast, United
1
2
Kingdom ; Northern Ireland Cancer Centre, Belfast, United Kingdom ; and Queens University Belfast,
3
Belfast, United Kingdom
Advanced radiotherapy techniques such as intensity-modulated radiation therapy (IMRT) achieve
high levels of conformity to the tumor target volume through the sequential delivery of highly spatially
and temporally modulated radiation fields. Our laboratory has shown significant alterations in cell survival
occurring outside of the primary field which cannot be accounted for on the basis of scattered dose and
may impact significantly on clinical treatment planning scenarios. This study aimed to further characterise
radiobiological responses to modulated fields focussing on signalling effects within the tumor
microenvironment and the determining role of DNA repair. Cell survival was determined by clonogenic
assay using human prostate (DU145), lung (H460) and transformed fibroblast (AG0-1522) cells following
exposure to modulated radiation fields delivered using a X-Rad 225 x-ray generator. In-field responses
were shown to be oxygen dependent with no significant time dependency. Conversely, out-of-field
responses showed no oxygen dependency and reached a plateau level 6 hours after irradiation. Mixed co-
cultures of tumor and normal cell types showed differential responses depending on the irradiated cell
type. In addition, small molecule inhibitors of ATM and ATR kinases showed out-of-field responses to be
ATR but not ATM dependent. These data provide further insight into the radiobiological parameters
impacting on response to advanced radiotherapy modalities which may have important implications for
the biophysical optimization of radiotherapy by improving efficacy and reducing normal tissue
complication.
(PS4-68) Role of stroma-epithelial interactions for low dose radiation induced lung carcinogenesis. Anna
R. Acheva, PhD; Elina Lemola; Elina Eklund; Virpi Launonen; and Meerit Kämäräinen, Radiation and
Nuclear Safety Authority - STUK, Helsinki, Finland
Lung cancer is the most diagnosed cancer worldwide with 1.35 million new cases registered each
year. Smoking has been shown as the leading causative factor as the second place has been attributed to
ionizing radiation. We aimed to study the early effects of low dose (0.1 Gy) exposure to α-particle
irradiation, similar to the natural sources, using bronchial epithelial cell lines (BEAS-2B and HBEC-3KT) as
a model system. We focused on process known as EMT (epithelial-mesenchymal transition) which is
characterized by switch of epithelial polarized phenotype to mesenchymal phenotype leading to loss of
cell contacts and increased cell motility. The role of the exposure of normal tissue microenvironment
(stroma) has also been investigated using normal primary human fibroblasts (MRC-9) for model. We
239
performed acute α- ( Pu), and acute (1.13-1.15 Gy/min) and protracted (1.4 mGy/h or 14 mGy/h) γ-
272 | P a g e
dependent survival of tumor cells exposed to ionizing radiation and subsequent hypoxia of varying
severity and duration with the goal of improving scientific understanding of cellular and physiological
responses to single fraction, high dose irradiations such as those occurring during SRT.
(PS4-67) Defining the role of the tumor microenvironment and DNA repair in cell survival responses
1
following exposure to intensity-modulated radiation fields. Karl T. Butterworth, PhD ; Stephen J.
1;2
2
2
1
McMahon, PhD ; Conor K. McGarry, PhD ; Aidan J. Cole, MD ; Suneil Jain, M.B., B.Ch ; Joe M. O'Sullivan,
1
1;2
3;2
FRR(RCSI) ; Alan R. Hounsell, Phd ; and Kevin M. Prise, PhD, Queen's University Belfast, Belfast, United
1
2
Kingdom ; Northern Ireland Cancer Centre, Belfast, United Kingdom ; and Queens University Belfast,
3
Belfast, United Kingdom
Advanced radiotherapy techniques such as intensity-modulated radiation therapy (IMRT) achieve
high levels of conformity to the tumor target volume through the sequential delivery of highly spatially
and temporally modulated radiation fields. Our laboratory has shown significant alterations in cell survival
occurring outside of the primary field which cannot be accounted for on the basis of scattered dose and
may impact significantly on clinical treatment planning scenarios. This study aimed to further characterise
radiobiological responses to modulated fields focussing on signalling effects within the tumor
microenvironment and the determining role of DNA repair. Cell survival was determined by clonogenic
assay using human prostate (DU145), lung (H460) and transformed fibroblast (AG0-1522) cells following
exposure to modulated radiation fields delivered using a X-Rad 225 x-ray generator. In-field responses
were shown to be oxygen dependent with no significant time dependency. Conversely, out-of-field
responses showed no oxygen dependency and reached a plateau level 6 hours after irradiation. Mixed co-
cultures of tumor and normal cell types showed differential responses depending on the irradiated cell
type. In addition, small molecule inhibitors of ATM and ATR kinases showed out-of-field responses to be
ATR but not ATM dependent. These data provide further insight into the radiobiological parameters
impacting on response to advanced radiotherapy modalities which may have important implications for
the biophysical optimization of radiotherapy by improving efficacy and reducing normal tissue
complication.
(PS4-68) Role of stroma-epithelial interactions for low dose radiation induced lung carcinogenesis. Anna
R. Acheva, PhD; Elina Lemola; Elina Eklund; Virpi Launonen; and Meerit Kämäräinen, Radiation and
Nuclear Safety Authority - STUK, Helsinki, Finland
Lung cancer is the most diagnosed cancer worldwide with 1.35 million new cases registered each
year. Smoking has been shown as the leading causative factor as the second place has been attributed to
ionizing radiation. We aimed to study the early effects of low dose (0.1 Gy) exposure to α-particle
irradiation, similar to the natural sources, using bronchial epithelial cell lines (BEAS-2B and HBEC-3KT) as
a model system. We focused on process known as EMT (epithelial-mesenchymal transition) which is
characterized by switch of epithelial polarized phenotype to mesenchymal phenotype leading to loss of
cell contacts and increased cell motility. The role of the exposure of normal tissue microenvironment
(stroma) has also been investigated using normal primary human fibroblasts (MRC-9) for model. We
239
performed acute α- ( Pu), and acute (1.13-1.15 Gy/min) and protracted (1.4 mGy/h or 14 mGy/h) γ-
272 | P a g e
