Page 168 - 2014 Printable Abstract Book
P. 168
(PS2-57) Development of atherosclerotic plaques after acute and chronic low-dose irradiation of ApoE-
1
1
2
2
/- mice. Mariateresa Mancuso ; Emanuela Pasquali ; Ignacia Braga-Tanaka III ; Satoshi Tanaka ; Kevin
3
1
4
2
1
C.M. Gulay ; Alessandro Pannicelli ; Paola Giardullo ; Simonetta Pazzaglia ; Michael J. Atkinson ; Anna
1
Saran, Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie,
1
l’Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy ; Institute for Environmental Sciences
3
2
(IES), Rokkasho, Aomori, Japan ; Università Guglielmo Marconi, Rome, Italy ; and Institute of Radiation
Biology, Helmholtz Zentrum, München, Germany
4
Epidemiological evidence has established increased non-cancer mortality due to radiation
exposures. The most prominent cause of this increase is circulatory disease mortality at doses greater
than 0.5 Sv. Cardiovascular effects have been observed in irradiated cohorts of patients receiving radiation
treatments and also in professionally exposed workers; nevertheless, much remains to be clarified about
the influence of dose rate on the risks at low doses, as well as on the causal mechanisms.
In order to gain new insights on these aspects, we monitored atherosclerotic plaques development in a
mouse model predisposed to spontaneous atherogenesis (ApoE mice). When fed with a normal chow
-/-
diet (4.2% fat), these mice exhibit a marked increase in plasma cholesterol levels and develop
atherosclerotic lesions resembling those seen in humans. As a consequence, they represent an ideal
mouse model to establish, in vivo, whether ionizing radiation acts as initiator or promoter in the
atherogenic process. Groups of 60-day old ApoE female mice were chronically irradiated for 300 days
-/-
with X-rays delivered at two different dose-rates (1 mGy/day or 20 mGy/day) reaching a total final dose
of 0.3 or 6 Gy, respectively. Additional groups were subjected to acute exposure, receiving a single dose
of 0.3 or 6 Gy when they were 60-days old, then sacrificed after 300 days from irradiation. Sham-irradiated
ApoE females of the appropriate age were used as controls. Aortic trees were dissected and examined
-/-
by en face after staining with Oil-Red-O, then lesions were analyzed using a morphometric approach. A
-/-
statistically significant increase of atherogenesis in ApoE mice was observed in all irradiated animals;
however, mice irradiated chronically with a higher dose rate showed a dramatic increase in terms of
percentage of Oil Red O–stained area, indicating that the radiation intensity could be determinant in
atherosclerotic plaque progression. Experiments are in progress to establish the mechanisms involved in
radiation-induced atherogenesis. Supported by “PROCARDIO” project. This project has received funding
from the European Seventh Framework Programme under grant agreement n° 295823.
(PS2-58) Tumor cells, but not endothelial cells, mediate the eradication of primary cancers by radiation
therapy. Everett J. Moding; Chang-Lung Lee; Katherine D. Castle; David G. Kirsch, Duke University Medical
Center, Durham, NC
Radiation therapy is frequently utilized in the clinic as curative treatment for cancers. Human
cancers develop in a complex environment composed of blood vessels, fibroblasts, and immune cells.
However, it remains controversial whether stromal cells, such as endothelial cells, or tumor cells are the
critical targets that regulate tumor eradication by radiation therapy. Genetically engineered mouse
models of cancer develop within a native tumor microenvironment in immunocompetent mice and may
more faithfully recapitulate the tumor microenvironment of human cancer compared to transplanted
models. To determine the critical target(s) in primary tumors that mediate local control by radiation
therapy, we used dual recombinase technology to selectively manipulate the radiosensitivity of
endothelial cells or tumors cells in a genetically engineered mouse model of soft tissue sarcoma. We
166 | P a g e
1
1
2
2
/- mice. Mariateresa Mancuso ; Emanuela Pasquali ; Ignacia Braga-Tanaka III ; Satoshi Tanaka ; Kevin
3
1
4
2
1
C.M. Gulay ; Alessandro Pannicelli ; Paola Giardullo ; Simonetta Pazzaglia ; Michael J. Atkinson ; Anna
1
Saran, Laboratory of Radiation Biology and Biomedicine, Agenzia Nazionale per le Nuove Tecnologie,
1
l’Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy ; Institute for Environmental Sciences
3
2
(IES), Rokkasho, Aomori, Japan ; Università Guglielmo Marconi, Rome, Italy ; and Institute of Radiation
Biology, Helmholtz Zentrum, München, Germany
4
Epidemiological evidence has established increased non-cancer mortality due to radiation
exposures. The most prominent cause of this increase is circulatory disease mortality at doses greater
than 0.5 Sv. Cardiovascular effects have been observed in irradiated cohorts of patients receiving radiation
treatments and also in professionally exposed workers; nevertheless, much remains to be clarified about
the influence of dose rate on the risks at low doses, as well as on the causal mechanisms.
In order to gain new insights on these aspects, we monitored atherosclerotic plaques development in a
mouse model predisposed to spontaneous atherogenesis (ApoE mice). When fed with a normal chow
-/-
diet (4.2% fat), these mice exhibit a marked increase in plasma cholesterol levels and develop
atherosclerotic lesions resembling those seen in humans. As a consequence, they represent an ideal
mouse model to establish, in vivo, whether ionizing radiation acts as initiator or promoter in the
atherogenic process. Groups of 60-day old ApoE female mice were chronically irradiated for 300 days
-/-
with X-rays delivered at two different dose-rates (1 mGy/day or 20 mGy/day) reaching a total final dose
of 0.3 or 6 Gy, respectively. Additional groups were subjected to acute exposure, receiving a single dose
of 0.3 or 6 Gy when they were 60-days old, then sacrificed after 300 days from irradiation. Sham-irradiated
ApoE females of the appropriate age were used as controls. Aortic trees were dissected and examined
-/-
by en face after staining with Oil-Red-O, then lesions were analyzed using a morphometric approach. A
-/-
statistically significant increase of atherogenesis in ApoE mice was observed in all irradiated animals;
however, mice irradiated chronically with a higher dose rate showed a dramatic increase in terms of
percentage of Oil Red O–stained area, indicating that the radiation intensity could be determinant in
atherosclerotic plaque progression. Experiments are in progress to establish the mechanisms involved in
radiation-induced atherogenesis. Supported by “PROCARDIO” project. This project has received funding
from the European Seventh Framework Programme under grant agreement n° 295823.
(PS2-58) Tumor cells, but not endothelial cells, mediate the eradication of primary cancers by radiation
therapy. Everett J. Moding; Chang-Lung Lee; Katherine D. Castle; David G. Kirsch, Duke University Medical
Center, Durham, NC
Radiation therapy is frequently utilized in the clinic as curative treatment for cancers. Human
cancers develop in a complex environment composed of blood vessels, fibroblasts, and immune cells.
However, it remains controversial whether stromal cells, such as endothelial cells, or tumor cells are the
critical targets that regulate tumor eradication by radiation therapy. Genetically engineered mouse
models of cancer develop within a native tumor microenvironment in immunocompetent mice and may
more faithfully recapitulate the tumor microenvironment of human cancer compared to transplanted
models. To determine the critical target(s) in primary tumors that mediate local control by radiation
therapy, we used dual recombinase technology to selectively manipulate the radiosensitivity of
endothelial cells or tumors cells in a genetically engineered mouse model of soft tissue sarcoma. We
166 | P a g e
