Page 308 - 2014 Printable Abstract Book
P. 308
analysed the repair capacity and survival of ex-vivo irradiated primary skin fibroblasts of 5 dysmorphic
and/or developmentally delayed paediatric patients with combined (T and B cell) immunodeficiency. Non-
linear regression analysis of γ-H2AX foci formation and resolution in response to ex-vivo irradiation
revealed that a slower repair rate and larger residual component are the most critical parameters in
identification of RS and provided an important opportunity to establish RS status of the patients prior to
commencement of conditioning. We present these values on a diagram that shows each patient as a point
in a two-dimensional “RS map”. These results were in agreement with assessment of cellular RS by
clonogenic survival, and with NHEJ genetic analysis. In a 6 year old boy, the γ-H2AX foci analysis fit the RS
status on the map, and the shape of repair kinetics suggested Ligase IV or XLF deficiency. Sequencing of
the LIGIV gene subsequently identified compound heterozygous mutations (c.845A>T, p.H282L and
c.73C>T, p.R25X). Timely and accurate identification of such patients can reduce therapy-related severe
side effects, by selection of the most appropriate conditioning regimen.
(PS5-37) Mitochondrial DNA changes in NIH Swiss mice exposed to low-dose gamma and proton
radiation. Steven B. Zhang, DVM, PhD; Liangjie Yin, MS; Zhenhuan Zhang, MD, PhD; Amy Zhang, MS; Mei
Zhang, MD; Shanmin Yang, MD; Chaomei Liu, PhD; Steven G. Swarts, PhD; Sadasivan Vidyasagar, MD, PhD;
and Paul Okunieff, MD, UF Shands Cancer Center, Gainesville, FL
Objective: Mitochondrial function and mitochondrial DNA (mtDNA) respond acutely and
chronically to radiation exposure. Abnormal mtDNA can have important long-term effects on organ and
organism health. Proton radiation might have a different impact on mtDNA biogenesis than photon
radiation; however, this difference might not be detected in cell survival studies. Therefore, we studied
the mitochondrial response of tissues from mice exposed to photons (gamma rays) and protons.
Methods: NIH Swiss mice received various whole-body doses (0, 0.5, 1, and 1.5 Gy) of gamma and spread-
out Bragg peak protons. mtDNA content and common deletion mutation rates were measured in the
heart, liver, lung, kidney, spleen, bone marrow, gut, and brain tissues 5 days after irradiation.
Results: The radiation response of mtDNA varied between different tissues. Gamma radiation resulted in
significant decreases of mtDNA content in the liver, lung, kidney, spleen, and gut. mtDNA was not
significantly changed in the bone marrow, heart, and brain. Proton radiation resulted in significant
decreases of mtDNA content in the lung and gut. At 0.5 Gy, protons significantly increased mtDNA changes
in the heart, liver, spleen, and brain. Protons did not induce a change in mtDNA in the kidney or bone
marrow. Dose-dependent mtDNA changes were found only in the proton-irradiated liver and spleen. A
significant increase in the mtDNA common deletion was found in the proton-irradiated liver.
Conclusion: This study compared, for the first time, the low-dose effects of photons and protons on the
mtDNA response of different organs. Our results indicate there are differences between tissues and
differences related to radiation quality. These findings should prove relevant to the prediction of late
effects in patients undergoing proton therapy and to astronauts exposed to cosmic or solar radiation.
(PS5-38) Time of inspiration to time of expiration ratio as a new respiratory parameter in assessment
of radiation induced lung injury. Shabnam Salimi, MD,Msc; Puting Xu, MD; Isabel L. Jackson, PhD; and
Zeljko Vujaskovic, MD, PhD; University of Maryland, Baltimore, School of Medicine, Department of
Radiation Oncology, Division of Translational Radiation Sciences, Baltimore, MD
Background: Under normal physiological condition, time of expiration (Te) is longer than time of
inspiration (Ti). However, in situations of respiratory insufficiency, inspiration takes longer than expiration
306 | P a g e
and/or developmentally delayed paediatric patients with combined (T and B cell) immunodeficiency. Non-
linear regression analysis of γ-H2AX foci formation and resolution in response to ex-vivo irradiation
revealed that a slower repair rate and larger residual component are the most critical parameters in
identification of RS and provided an important opportunity to establish RS status of the patients prior to
commencement of conditioning. We present these values on a diagram that shows each patient as a point
in a two-dimensional “RS map”. These results were in agreement with assessment of cellular RS by
clonogenic survival, and with NHEJ genetic analysis. In a 6 year old boy, the γ-H2AX foci analysis fit the RS
status on the map, and the shape of repair kinetics suggested Ligase IV or XLF deficiency. Sequencing of
the LIGIV gene subsequently identified compound heterozygous mutations (c.845A>T, p.H282L and
c.73C>T, p.R25X). Timely and accurate identification of such patients can reduce therapy-related severe
side effects, by selection of the most appropriate conditioning regimen.
(PS5-37) Mitochondrial DNA changes in NIH Swiss mice exposed to low-dose gamma and proton
radiation. Steven B. Zhang, DVM, PhD; Liangjie Yin, MS; Zhenhuan Zhang, MD, PhD; Amy Zhang, MS; Mei
Zhang, MD; Shanmin Yang, MD; Chaomei Liu, PhD; Steven G. Swarts, PhD; Sadasivan Vidyasagar, MD, PhD;
and Paul Okunieff, MD, UF Shands Cancer Center, Gainesville, FL
Objective: Mitochondrial function and mitochondrial DNA (mtDNA) respond acutely and
chronically to radiation exposure. Abnormal mtDNA can have important long-term effects on organ and
organism health. Proton radiation might have a different impact on mtDNA biogenesis than photon
radiation; however, this difference might not be detected in cell survival studies. Therefore, we studied
the mitochondrial response of tissues from mice exposed to photons (gamma rays) and protons.
Methods: NIH Swiss mice received various whole-body doses (0, 0.5, 1, and 1.5 Gy) of gamma and spread-
out Bragg peak protons. mtDNA content and common deletion mutation rates were measured in the
heart, liver, lung, kidney, spleen, bone marrow, gut, and brain tissues 5 days after irradiation.
Results: The radiation response of mtDNA varied between different tissues. Gamma radiation resulted in
significant decreases of mtDNA content in the liver, lung, kidney, spleen, and gut. mtDNA was not
significantly changed in the bone marrow, heart, and brain. Proton radiation resulted in significant
decreases of mtDNA content in the lung and gut. At 0.5 Gy, protons significantly increased mtDNA changes
in the heart, liver, spleen, and brain. Protons did not induce a change in mtDNA in the kidney or bone
marrow. Dose-dependent mtDNA changes were found only in the proton-irradiated liver and spleen. A
significant increase in the mtDNA common deletion was found in the proton-irradiated liver.
Conclusion: This study compared, for the first time, the low-dose effects of photons and protons on the
mtDNA response of different organs. Our results indicate there are differences between tissues and
differences related to radiation quality. These findings should prove relevant to the prediction of late
effects in patients undergoing proton therapy and to astronauts exposed to cosmic or solar radiation.
(PS5-38) Time of inspiration to time of expiration ratio as a new respiratory parameter in assessment
of radiation induced lung injury. Shabnam Salimi, MD,Msc; Puting Xu, MD; Isabel L. Jackson, PhD; and
Zeljko Vujaskovic, MD, PhD; University of Maryland, Baltimore, School of Medicine, Department of
Radiation Oncology, Division of Translational Radiation Sciences, Baltimore, MD
Background: Under normal physiological condition, time of expiration (Te) is longer than time of
inspiration (Ti). However, in situations of respiratory insufficiency, inspiration takes longer than expiration
306 | P a g e
