Page 227 - 2014 Printable Abstract Book
P. 227
3
Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR ; and Surgical
4
Service, Central Arkansas Veterans Healthcare System, Little Rock, AR
Radiation therapy is frequently used to treat malignant conditions either alone or concomitant
with other modalities. Skin tissue is a major recipient of significant collateral damage during radiotherapy.
Approximately 95% of patients who have had radiotherapy suffer from both acute and chronic side
effects. Thus, despite discoveries in radiation biology and improvements in radiation technology, there is
still a significant need for a safe and effective radioprotector /radiomitigator compound to alleviate the
side effects of radiotherapy on skin tissue. One of the few and most promising alternatives is the vitamin
E analogs δ-tocotrienol (DT3) and -tocotrienol (GT3). These compounds have shown significant
radioprotectant and radiomitigator activities with minimal side effects. Unfortunately, both compounds
are in short supply and very expensive to purify. Rice bran oil deodorizer distillate (RBODD), a byproduct
in the refinement of rice oil, contains large amounts of tocotrienols. In this study, we hypothesized that
RBODD can protect mitochondrial function and oxidative metabolism and thus safeguard skin cells from
radiation injury. We have compared the effects of DT3 and RBODD against radiation induced
mitochondrial dysfunction and oxidative stress in human skin cells. Our data demonstrated that IR
exposed cells treated with 5 μM DT3 or RBODD preserved the clonogenic cell survival and mitochondrial
function. Furthermore, treatment of skin keratinocytes with 5 μM DT3 or RBODD protected the cell
morphology and improved migration rates observed in scratch assays, even though the cells were treated
with tocotrienols 4 h after the IR exposure. These preliminary results indicate that RBODD is potentially a
viable source for tocotrienols that can be used as radioprotectors. (This work is funded by Master Tobacco
Settlement Funds administered through the Arkansas Biosciences Institute)
(PS3-70) Directional genomic hybridization as a potential metric in assessing past radiation exposures
2
1;2
2
2;1
to US veterans. Miles J. McKenna ; Erin Robinson ; F. Andrew Ray ; Christopher Tompkins ; Michael
1;2
4
3
Cornforth ; Steven L. Simon ; and Susan M. Bailey ;Department of Environmental and Radiological
2
1
Health Sciences, Colorado State University, Fort Collins, CO ; KromaTiD, Inc., Fort Collins, CO ; University
3
of Texas Medical Branch, Galveston, TX ; and National Cancer Institute, National Institutes of Health,
Bethesda, MD
4
Radiation exposure of the public is recognized today as an unwanted consequence of accidents
and terrorist events. Reliable assessment methods are needed to evaluate past exposures to allow for
proper medical care and risk evaluation. Dicentric and micronuclei analyses have long been recognized as
the standards for biodosimetric assessments, but both suffer a major drawback in that they are unstable
with time following exposure. Because they are more stable with time postirradiation, symmetrical
aberrations - such as reciprocal translocations and inversions - are more suitable for this task.
Shortcomings of translocations in this setting are that they are present at relatively high frequency in
unexposed populations, and their frequencies are known to increase in response to a number of
environmental factors unrelated to radiation. Due to their predictably stable nature, and higher yields per
unit dose, inversions therefore provide an attractive alternative biodosimetric endpoint.
A new cytogenetic technique has been developed to analyze inversion frequencies―which, to the best of
our knowledge have never been used for biodosimetry― utilizing a strand specific fluorescent in situ
hybridization platform termed directional genomic hybridization (dGH). dGH is capable of detecting
smaller inversions than current cytogenetic techniques allow, and thus potentially provides a more robust
225 | P a g e
Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR ; and Surgical
4
Service, Central Arkansas Veterans Healthcare System, Little Rock, AR
Radiation therapy is frequently used to treat malignant conditions either alone or concomitant
with other modalities. Skin tissue is a major recipient of significant collateral damage during radiotherapy.
Approximately 95% of patients who have had radiotherapy suffer from both acute and chronic side
effects. Thus, despite discoveries in radiation biology and improvements in radiation technology, there is
still a significant need for a safe and effective radioprotector /radiomitigator compound to alleviate the
side effects of radiotherapy on skin tissue. One of the few and most promising alternatives is the vitamin
E analogs δ-tocotrienol (DT3) and -tocotrienol (GT3). These compounds have shown significant
radioprotectant and radiomitigator activities with minimal side effects. Unfortunately, both compounds
are in short supply and very expensive to purify. Rice bran oil deodorizer distillate (RBODD), a byproduct
in the refinement of rice oil, contains large amounts of tocotrienols. In this study, we hypothesized that
RBODD can protect mitochondrial function and oxidative metabolism and thus safeguard skin cells from
radiation injury. We have compared the effects of DT3 and RBODD against radiation induced
mitochondrial dysfunction and oxidative stress in human skin cells. Our data demonstrated that IR
exposed cells treated with 5 μM DT3 or RBODD preserved the clonogenic cell survival and mitochondrial
function. Furthermore, treatment of skin keratinocytes with 5 μM DT3 or RBODD protected the cell
morphology and improved migration rates observed in scratch assays, even though the cells were treated
with tocotrienols 4 h after the IR exposure. These preliminary results indicate that RBODD is potentially a
viable source for tocotrienols that can be used as radioprotectors. (This work is funded by Master Tobacco
Settlement Funds administered through the Arkansas Biosciences Institute)
(PS3-70) Directional genomic hybridization as a potential metric in assessing past radiation exposures
2
1;2
2
2;1
to US veterans. Miles J. McKenna ; Erin Robinson ; F. Andrew Ray ; Christopher Tompkins ; Michael
1;2
4
3
Cornforth ; Steven L. Simon ; and Susan M. Bailey ;Department of Environmental and Radiological
2
1
Health Sciences, Colorado State University, Fort Collins, CO ; KromaTiD, Inc., Fort Collins, CO ; University
3
of Texas Medical Branch, Galveston, TX ; and National Cancer Institute, National Institutes of Health,
Bethesda, MD
4
Radiation exposure of the public is recognized today as an unwanted consequence of accidents
and terrorist events. Reliable assessment methods are needed to evaluate past exposures to allow for
proper medical care and risk evaluation. Dicentric and micronuclei analyses have long been recognized as
the standards for biodosimetric assessments, but both suffer a major drawback in that they are unstable
with time following exposure. Because they are more stable with time postirradiation, symmetrical
aberrations - such as reciprocal translocations and inversions - are more suitable for this task.
Shortcomings of translocations in this setting are that they are present at relatively high frequency in
unexposed populations, and their frequencies are known to increase in response to a number of
environmental factors unrelated to radiation. Due to their predictably stable nature, and higher yields per
unit dose, inversions therefore provide an attractive alternative biodosimetric endpoint.
A new cytogenetic technique has been developed to analyze inversion frequencies―which, to the best of
our knowledge have never been used for biodosimetry― utilizing a strand specific fluorescent in situ
hybridization platform termed directional genomic hybridization (dGH). dGH is capable of detecting
smaller inversions than current cytogenetic techniques allow, and thus potentially provides a more robust
225 | P a g e
