Page 161 - 2014 Printable Abstract Book
P. 161
(PS2-44) Organ-specific total body irradiation (tbi) induction of RNA transcripts in mnsod tet/tet mice.
Byung Han Rhieu; Ashwin Shinde; Michael Epperly; Tracy Dixon; Darcy Franicola; Julie Goff; Xichen Zhang;
Hong Wang; Richard Chaillet; and Joel S. Greenberger, University of Pittsburgh, Pittsburgh, PA
Purpose/Objectives: MnSOD tet/tet mice show doxycycline (doxy) induced protein (Epperly et al;
Radiation Research 2013; 180(2):189-204). We compared total body irradiation (TBI) induced RNA
transcripts in 11 organs. Materials/Methods: Six week old male and female MnSOD tet/tet and wild type
C57Bl6/HNsd mice (4 per group) received doxy in food. At day 19 mice were sacrificed, tissues harvested,
RNA extracted, and transcripts quantitated by real time (rt) PCR, and expressed as % change over baseline.
Results: Ten of 11 doxy treated MnSOD tet/tet mouse organs (except intestine) showed lower levels of
MnSOD than wild type mice (p= <0.05). Intestine of doxy MnSOD tet/tet mice had higher MnSOD levels
(614.64±55.98, p= <0.05). After TBI, MnSOD in 10 organs of tet/tet mice (except intestine) remained low
(P= <0.05). GPX1 in Brain, muscle, and spleen of doxy treated MnSOD tet/tet mice was higher than did
wild type (P= <0.05) but lower in esophagus intestine, kidney, and tongue (p=<0.05). After TBI, GPX1
increased in intestine. Nrf2 increased in liver and muscle of doxy treated tet/tet mice.
Conclusions: MnSOD tet/tet mouse organs demonstrate organ-specific differences in irradiation induction
of MnSOD. These mice should be valuable for study of regulation of antioxidant responses to TBI.
1
(PS2-45) Ptch1 heterozygous mice as a model for radiation cataractogenesis. Paola Giardullo ; Ilaria De
2
2
2
2
1
2
Stefano ; Barbara Tanno ; Simona Leonardi ; Emanuela Pasquali ; Francesca Antonelli ; Mirella Tanori ;
2
2
2
2
Arianna Casciati ; Simonetta Pazzaglia ; Anna Saran ; and Mariateresa Mancuso, Department of Radiation
1
Physics, Guglielmo Marconi University, Rome, Italy and Laboratory of Radiation Biology and Biomedicine,
Agenzia Nazionale per le Nuove Tecnologie, l’Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome,
2
Italy
Whilst most of the evidence for late health effects following radiation exposure relates to the
induction of cancer, there has been increasing interest in recent years in the development of non-cancer
diseases, including lens opacity, observed in populations exposed to low doses of radiation. Here, we
+/-
propose the Patched1 (Ptch1 ) heterozygous mice as a relevant mouse model of radiation-induced
cataract and demonstrate a key role of Sonic hedgehog (Shh) pathway in the molecular mechanisms
controlling cataract development. By irradiating mice at different postnatal ages with 3 Gy of X rays, we
observed virtual lack of radio-induced cataract when radiation was delivered at postnatal day (P) 10 and
P56; on the contrary, a highly statistically significant increase in cataract development, classified as
+/-
anterior subcapsular cataract (ASC), was observed in Ptch1 mice irradiated at P2 compared to
unirradiated mice (P < 0.0001). These data clearly indicate a strong age-dependent sensitivity to radiation
during the early stage of postnatal lens development, suggesting a synergism between Shh signaling
pathway deregulation and ionizing radiation, leading to an aberrant epithelial-mesenchymal transition
(EMT) induction. After a thorough study of lens epithelial cells (LECs) at P2 and at different times after
irradiation, we found a link between proliferation and the stemness property of LECs, strictly controlled
by Shh signaling pathway. A positive feedback loop between SHH and TGFβ signaling activating EMT is the
elective molecular mechanism driving cataract development after irradiation, with Nanog acting as the
most important transcription factor on which both signaling pathways converge after irradiation. Our
results add new insights into this emerging area of research and will facilitate future studies focused on
159 | P a g e
Byung Han Rhieu; Ashwin Shinde; Michael Epperly; Tracy Dixon; Darcy Franicola; Julie Goff; Xichen Zhang;
Hong Wang; Richard Chaillet; and Joel S. Greenberger, University of Pittsburgh, Pittsburgh, PA
Purpose/Objectives: MnSOD tet/tet mice show doxycycline (doxy) induced protein (Epperly et al;
Radiation Research 2013; 180(2):189-204). We compared total body irradiation (TBI) induced RNA
transcripts in 11 organs. Materials/Methods: Six week old male and female MnSOD tet/tet and wild type
C57Bl6/HNsd mice (4 per group) received doxy in food. At day 19 mice were sacrificed, tissues harvested,
RNA extracted, and transcripts quantitated by real time (rt) PCR, and expressed as % change over baseline.
Results: Ten of 11 doxy treated MnSOD tet/tet mouse organs (except intestine) showed lower levels of
MnSOD than wild type mice (p= <0.05). Intestine of doxy MnSOD tet/tet mice had higher MnSOD levels
(614.64±55.98, p= <0.05). After TBI, MnSOD in 10 organs of tet/tet mice (except intestine) remained low
(P= <0.05). GPX1 in Brain, muscle, and spleen of doxy treated MnSOD tet/tet mice was higher than did
wild type (P= <0.05) but lower in esophagus intestine, kidney, and tongue (p=<0.05). After TBI, GPX1
increased in intestine. Nrf2 increased in liver and muscle of doxy treated tet/tet mice.
Conclusions: MnSOD tet/tet mouse organs demonstrate organ-specific differences in irradiation induction
of MnSOD. These mice should be valuable for study of regulation of antioxidant responses to TBI.
1
(PS2-45) Ptch1 heterozygous mice as a model for radiation cataractogenesis. Paola Giardullo ; Ilaria De
2
2
2
2
1
2
Stefano ; Barbara Tanno ; Simona Leonardi ; Emanuela Pasquali ; Francesca Antonelli ; Mirella Tanori ;
2
2
2
2
Arianna Casciati ; Simonetta Pazzaglia ; Anna Saran ; and Mariateresa Mancuso, Department of Radiation
1
Physics, Guglielmo Marconi University, Rome, Italy and Laboratory of Radiation Biology and Biomedicine,
Agenzia Nazionale per le Nuove Tecnologie, l’Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome,
2
Italy
Whilst most of the evidence for late health effects following radiation exposure relates to the
induction of cancer, there has been increasing interest in recent years in the development of non-cancer
diseases, including lens opacity, observed in populations exposed to low doses of radiation. Here, we
+/-
propose the Patched1 (Ptch1 ) heterozygous mice as a relevant mouse model of radiation-induced
cataract and demonstrate a key role of Sonic hedgehog (Shh) pathway in the molecular mechanisms
controlling cataract development. By irradiating mice at different postnatal ages with 3 Gy of X rays, we
observed virtual lack of radio-induced cataract when radiation was delivered at postnatal day (P) 10 and
P56; on the contrary, a highly statistically significant increase in cataract development, classified as
+/-
anterior subcapsular cataract (ASC), was observed in Ptch1 mice irradiated at P2 compared to
unirradiated mice (P < 0.0001). These data clearly indicate a strong age-dependent sensitivity to radiation
during the early stage of postnatal lens development, suggesting a synergism between Shh signaling
pathway deregulation and ionizing radiation, leading to an aberrant epithelial-mesenchymal transition
(EMT) induction. After a thorough study of lens epithelial cells (LECs) at P2 and at different times after
irradiation, we found a link between proliferation and the stemness property of LECs, strictly controlled
by Shh signaling pathway. A positive feedback loop between SHH and TGFβ signaling activating EMT is the
elective molecular mechanism driving cataract development after irradiation, with Nanog acting as the
most important transcription factor on which both signaling pathways converge after irradiation. Our
results add new insights into this emerging area of research and will facilitate future studies focused on
159 | P a g e
