Page 112 - 2014 Printable Abstract Book
P. 112
(PS1-15) Ionizing radiation effects on Lake Whitefish embryonic development. Chris Thome; Charles
Mitz; and Douglas Boreham, McMaster University, Hamilton, Canada
Lake Whitefish (Coregonus clupeaformis) are a demersal freshwater fish which spawns in late fall.
Embryos develop throughout the winter months in the inshore rocky substrate, in areas potentially
impacted by discharges from nuclear or other generating stations. The purpose of this study is to
investigate the effects of ionizing radiation exposure on Lake Whitefish embryonic development. In-vitro
fertilization was performed on gametes collected from spawning adults in eastern Lake Huron. Embryos
were raised at a constant temperature in a static water incubation system, from fertilization until hatch.
137
At numerous points throughout development Cs gamma rays were delivered with doses ranging from
10 mGy up to 20 Gy. Embryos showed a high resistance to radiation induced mortality, with an LD50 of 2.7
Gy immediately post fertilization, increasing exponentially to 35 Gy by the midpoint of development.
Lower, sublethal doses resulted in a reduction in development period and accelerated the time until
hatch. In addition, embryos exposed on day 1 and 7 post fertilization showed a decrease in larval size. The
impacts of ionizing radiation are also being investigated in conjunction with other environmental
stressors. Development is currently being followed in embryos exposed to radiation along with thermal
stress and the chemicals morpholine and hypochlorite, commonly found in industrial coolant water
discharges. As well, the genotoxic effects of radiation exposure, specifically in the low dose region, is
currently being examined on a cellular level utilizing primary cultures derived from Lake Whitefish
embryos.
(PS1-17) The role of inflammation in radiation-induced genomic instability. Paul W. Doetsch; Erica
Werner; K X. Tang; and Huichen Wang. Emory University School of Medicine, Atlanta, GA
Previous findings in our laboratory revealed that exposure of normal human bronchial epithelial
cells to a single dose of 1 Gy of low (X-rays) or high (Fe ions) LET radiation induces a persistent stress
response, which includes reactive oxygen species (ROS) and nitric oxide (NO) production, senescence and
pro-inflammatory markers as well as genomic instability expressed as increased mironucleus frequency
and gamma-H2AX-53BP1 foci. All of these phenotypes are transient as they disappear by 2 weeks. Some
of these, such as elevated reactive oxygen species (ROS) and nitric oxide are radiation quality
independent, while genomic instability and the appearance of senescence and pro-inflammatory
biomarkers are radiation quality and dose dependent. We hypothesized that pro-inflammatory responses
mediate increased ROS and NO production and thereby could also promote genomic instability. To test
this hypothesis, we analyzed the release of inflammatory cytokines from cells at day 7 following exposure
to low and high LET radiation using an antibody array to profile the expression of 36 human cytokines. We
found multiple cytokines induced, including GM-CSF, IL1-alpha and beta, IL-1RA, IL-8, but not IFN gamma,
IL-6 or TNF alpha. Among these, IL-1 is a cytokine driving pro-inflammatory responses, thus we tested
whether exogenously added IL-1 Receptor Antagonist, a natural competitor for binding to IL-1 receptor,
reduces the induction of this response and whether it affects genomic instability. We found that
interference with IL-1 function using the antagonist prevented the induction of IL-8, but did not affect
genomic instability. Consistent with this mechanism, addition of IL-1 to non-irradiated cells was sufficient
to induce cytokine production, without inducing the expression of genomic instability markers or
promoting their expression in irradiated cells. We conclude that exposure of normal epithelial cells to 3-6
Gy low LET or to 1 Gy high LET radiation induces the production of IL-1, which promotes the release of
110 | P a g e
Mitz; and Douglas Boreham, McMaster University, Hamilton, Canada
Lake Whitefish (Coregonus clupeaformis) are a demersal freshwater fish which spawns in late fall.
Embryos develop throughout the winter months in the inshore rocky substrate, in areas potentially
impacted by discharges from nuclear or other generating stations. The purpose of this study is to
investigate the effects of ionizing radiation exposure on Lake Whitefish embryonic development. In-vitro
fertilization was performed on gametes collected from spawning adults in eastern Lake Huron. Embryos
were raised at a constant temperature in a static water incubation system, from fertilization until hatch.
137
At numerous points throughout development Cs gamma rays were delivered with doses ranging from
10 mGy up to 20 Gy. Embryos showed a high resistance to radiation induced mortality, with an LD50 of 2.7
Gy immediately post fertilization, increasing exponentially to 35 Gy by the midpoint of development.
Lower, sublethal doses resulted in a reduction in development period and accelerated the time until
hatch. In addition, embryos exposed on day 1 and 7 post fertilization showed a decrease in larval size. The
impacts of ionizing radiation are also being investigated in conjunction with other environmental
stressors. Development is currently being followed in embryos exposed to radiation along with thermal
stress and the chemicals morpholine and hypochlorite, commonly found in industrial coolant water
discharges. As well, the genotoxic effects of radiation exposure, specifically in the low dose region, is
currently being examined on a cellular level utilizing primary cultures derived from Lake Whitefish
embryos.
(PS1-17) The role of inflammation in radiation-induced genomic instability. Paul W. Doetsch; Erica
Werner; K X. Tang; and Huichen Wang. Emory University School of Medicine, Atlanta, GA
Previous findings in our laboratory revealed that exposure of normal human bronchial epithelial
cells to a single dose of 1 Gy of low (X-rays) or high (Fe ions) LET radiation induces a persistent stress
response, which includes reactive oxygen species (ROS) and nitric oxide (NO) production, senescence and
pro-inflammatory markers as well as genomic instability expressed as increased mironucleus frequency
and gamma-H2AX-53BP1 foci. All of these phenotypes are transient as they disappear by 2 weeks. Some
of these, such as elevated reactive oxygen species (ROS) and nitric oxide are radiation quality
independent, while genomic instability and the appearance of senescence and pro-inflammatory
biomarkers are radiation quality and dose dependent. We hypothesized that pro-inflammatory responses
mediate increased ROS and NO production and thereby could also promote genomic instability. To test
this hypothesis, we analyzed the release of inflammatory cytokines from cells at day 7 following exposure
to low and high LET radiation using an antibody array to profile the expression of 36 human cytokines. We
found multiple cytokines induced, including GM-CSF, IL1-alpha and beta, IL-1RA, IL-8, but not IFN gamma,
IL-6 or TNF alpha. Among these, IL-1 is a cytokine driving pro-inflammatory responses, thus we tested
whether exogenously added IL-1 Receptor Antagonist, a natural competitor for binding to IL-1 receptor,
reduces the induction of this response and whether it affects genomic instability. We found that
interference with IL-1 function using the antagonist prevented the induction of IL-8, but did not affect
genomic instability. Consistent with this mechanism, addition of IL-1 to non-irradiated cells was sufficient
to induce cytokine production, without inducing the expression of genomic instability markers or
promoting their expression in irradiated cells. We conclude that exposure of normal epithelial cells to 3-6
Gy low LET or to 1 Gy high LET radiation induces the production of IL-1, which promotes the release of
110 | P a g e
