Page 240 - 2014 Printable Abstract Book
P. 240
(PS4-10) Dynamics of hematopoietic stem cells and progenitors in C3H mice chronically irradiated at
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low dose rate. Part II. Mitsuaki Ojima ; Tokuhisa Hirouchi ; Junya Ishikawa ; Nobuhiko Ban ; Shizue Izumi ;
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and Michiaki Kai, Oita university of Nursing and Health Sciences, Oita, Japan ; Institute for Environmental
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Sciences, Rokkasho, Japan ; Tokyo Healthcare University, Meguro, Japan ; and Department of Computer
Science and Intelligent Systems, Oita University, Oita, Japan 4
A dose-rate effect (DRE) is a key phenomenon in radiation carcinogenesis for estimating radiation-
related cancer risk. Radiation biology has not yet clarified the picture of DRE in radiation carcinogenesis.
Exposure to ionizing radiation (IR) leads to acute myeloid leukemia (AML) in C3H mice after an incubation
period of between 1 to 2 years. In most IR-induced AML in C3H mice, hematopoietic stem cells (HSCs)
have both deletion around the PU.1 gene on chromosome 2 and a point mutation on PU.1 gene on
homologous chromosome 2. However, it has not been well understood when and how these mutations
aberrations occur after IR-irradiation. In order to clarify the mechanism of IR-induced AML, we have to
investigate the long-term effect of IR on HSCs. IR damage HSCs by inducing apoptosis, since HSCs are
relatively sensitive to IR. Then, we thought that the normal HSCs, which escaped apoptosis, might be
activated cell turnover. It has been reported that cell turnover causes aging. The aged cell produces
accumulation of Reactive Oxygen Species (ROS), which induces damage to DNA. Therefore, our aim is to
validate a hypothesis that aging through IR-induced cell turnover can induce AML-related mutations. This
study examined the dose-rate response of Ki67, which shows up regulate of cell cycle, in HSCs and
progenitors of total-body irradiated C3H mice at 20 mGy/day, 200 mGy/day and 1000mGy/min. The
positive expression of Ki67 in HSC increased with time in both 20 mGy/day and 200 mGy/day. When we
focused on the same accumulated doses of 200mGy, the % of Ki67 positive HSCs by 20mGy/day was
smaller than 200mGy/day. These results suggested that IR could induce aging through IR-induced cell
turnover and that IR can induce DRE of HSCs turnover. Our experimental data will produce a consistent
sight into the radiation DREs of HSCs turnover that would lead radiation leukaemogenesis.
(PS4-11) Topical tetrahydrocurcumin lotion reduces acute and late effects of combined radiation skin
injury. Julie L. Ryan, PhD, MPH; Julee Nanduri, MS; Margaret Barlow; Scott Gerber, PhD; Alice P. Pentland,
MD; and Edith M. Lord, PhD, University of Rochester Medical Center, Rochester, NY
Background: Combined radiation exposure induces both acute and late damage to the skin. We
tested the ability of topical 10% tetrahydrocurcumin (TH-curc) lotion to mitigate the acute and late effects
of combined radiation skin injury. Methods: Hairless C57BL6 mice were subjected to 1) 6 Gy TBI (Cs-137)
immediately followed by one (acute skin injury; N=6 per group) or two (late skin injury; N=5 per group) 40
Gy β burns (7.5 mm diameter Sr-90) on the back. Both models (TBI+β and TBI+2β) simulate localized
™
radiation exposure to the skin from fallout. Topical 10% TH-curc/Dermovan lotion (200 μl) was applied
to the back for seven consecutive days starting on Day 2 post-radiation. Acute skin injury measures
included transepidermal water loss (TEWL), acute skin toxicity scores, burn healing, and
inflammatory/antioxidant gene expression (RT-PCR). Late skin injury measures included skin elasticity and
2
skin retraction. Results: Topical TH-curc reduced TEWL and burn severity (TEWL, skin score = 15.60 g/m h,
2
™
2.36) following TBI+β compared to Dermovan -treated and untreated mice (20.28 g/m h, 3.83 and 27.68
2
g/m h, 3.30, respectively; p≤0.04). Additionally, TH-curc improved burn size and healing over time
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2
®
(maximum area [S.E.] = 49.37 mm [2.77] vs. 109.34 mm [12.93]; p<0.05). SYBR Green RT-PCR analyses
showed that TH-curc-treated skin had up-regulation of IL-10 and IL-4 and down-regulation of iNOS and
238 | P a g e
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3
1
2
1
low dose rate. Part II. Mitsuaki Ojima ; Tokuhisa Hirouchi ; Junya Ishikawa ; Nobuhiko Ban ; Shizue Izumi ;
1
1
and Michiaki Kai, Oita university of Nursing and Health Sciences, Oita, Japan ; Institute for Environmental
2
3
Sciences, Rokkasho, Japan ; Tokyo Healthcare University, Meguro, Japan ; and Department of Computer
Science and Intelligent Systems, Oita University, Oita, Japan 4
A dose-rate effect (DRE) is a key phenomenon in radiation carcinogenesis for estimating radiation-
related cancer risk. Radiation biology has not yet clarified the picture of DRE in radiation carcinogenesis.
Exposure to ionizing radiation (IR) leads to acute myeloid leukemia (AML) in C3H mice after an incubation
period of between 1 to 2 years. In most IR-induced AML in C3H mice, hematopoietic stem cells (HSCs)
have both deletion around the PU.1 gene on chromosome 2 and a point mutation on PU.1 gene on
homologous chromosome 2. However, it has not been well understood when and how these mutations
aberrations occur after IR-irradiation. In order to clarify the mechanism of IR-induced AML, we have to
investigate the long-term effect of IR on HSCs. IR damage HSCs by inducing apoptosis, since HSCs are
relatively sensitive to IR. Then, we thought that the normal HSCs, which escaped apoptosis, might be
activated cell turnover. It has been reported that cell turnover causes aging. The aged cell produces
accumulation of Reactive Oxygen Species (ROS), which induces damage to DNA. Therefore, our aim is to
validate a hypothesis that aging through IR-induced cell turnover can induce AML-related mutations. This
study examined the dose-rate response of Ki67, which shows up regulate of cell cycle, in HSCs and
progenitors of total-body irradiated C3H mice at 20 mGy/day, 200 mGy/day and 1000mGy/min. The
positive expression of Ki67 in HSC increased with time in both 20 mGy/day and 200 mGy/day. When we
focused on the same accumulated doses of 200mGy, the % of Ki67 positive HSCs by 20mGy/day was
smaller than 200mGy/day. These results suggested that IR could induce aging through IR-induced cell
turnover and that IR can induce DRE of HSCs turnover. Our experimental data will produce a consistent
sight into the radiation DREs of HSCs turnover that would lead radiation leukaemogenesis.
(PS4-11) Topical tetrahydrocurcumin lotion reduces acute and late effects of combined radiation skin
injury. Julie L. Ryan, PhD, MPH; Julee Nanduri, MS; Margaret Barlow; Scott Gerber, PhD; Alice P. Pentland,
MD; and Edith M. Lord, PhD, University of Rochester Medical Center, Rochester, NY
Background: Combined radiation exposure induces both acute and late damage to the skin. We
tested the ability of topical 10% tetrahydrocurcumin (TH-curc) lotion to mitigate the acute and late effects
of combined radiation skin injury. Methods: Hairless C57BL6 mice were subjected to 1) 6 Gy TBI (Cs-137)
immediately followed by one (acute skin injury; N=6 per group) or two (late skin injury; N=5 per group) 40
Gy β burns (7.5 mm diameter Sr-90) on the back. Both models (TBI+β and TBI+2β) simulate localized
™
radiation exposure to the skin from fallout. Topical 10% TH-curc/Dermovan lotion (200 μl) was applied
to the back for seven consecutive days starting on Day 2 post-radiation. Acute skin injury measures
included transepidermal water loss (TEWL), acute skin toxicity scores, burn healing, and
inflammatory/antioxidant gene expression (RT-PCR). Late skin injury measures included skin elasticity and
2
skin retraction. Results: Topical TH-curc reduced TEWL and burn severity (TEWL, skin score = 15.60 g/m h,
2
™
2.36) following TBI+β compared to Dermovan -treated and untreated mice (20.28 g/m h, 3.83 and 27.68
2
g/m h, 3.30, respectively; p≤0.04). Additionally, TH-curc improved burn size and healing over time
2
2
®
(maximum area [S.E.] = 49.37 mm [2.77] vs. 109.34 mm [12.93]; p<0.05). SYBR Green RT-PCR analyses
showed that TH-curc-treated skin had up-regulation of IL-10 and IL-4 and down-regulation of iNOS and
238 | P a g e
