Page 237 - 2014 Printable Abstract Book
P. 237
tumor cells, indicating increased CAF radioresistance. Data describing survival and cell cycle progression
of the irradiated cocultured tumor cells will also be presented. Together, the results show that CAFs
greatly affect the response of tumor cells. Further, the increased oxidative stress initiated by the cancer
cells, and the concomitant increase in antioxidant activity of CAFs, may drive CAFs’ formation and
contribute to their radioresistance through an adaptive response mechanism.
(PS4-04) Dynamics of hematopoietic stem cells and progenitors in C3H mice chronically irradiated at
1
2
2
low dose rate. Part I. Tokuhisa Hirouhi ; Mitsuaki Ojima ; Junya Ishikawa, assistant professor ; Nobuhiko
1
4
2
3
Ban ; Shizue Izumi ; and Michiaki Kai, Institute for Environmental Sciences, Rokkasho, Japan ; Oita
2
3
University of Nursing and Health Sciences, Oita, Japan ; Tokyo Healthcare University, Meguro, Japan ; and
4
Department of Computer Science and Intelligent Systems, Oita University, Oita, Japan
Objective: A dose-rate effect of radiation is important for estimating cancer risk, but a whole
picture of them has not been clarified. High-dose-rate ionizing radiation (IR) develops acute myeloid
leukemia in mice 1-2 years after irradiation. Continuous low-dose-rate IR also causes murine myeloid
leukemia. Chromosomal aberrations of leukemic cell in high- and low-dose-rate IR-induced leukemias are
apparently different. In order to clarify a mechanism causing the chromosomal differences, we
continuously investigated long-lived hematopoietic stem cells (HSCs) and progenitors during and after
irradiation. Methods: C3H mice were subjected to total-body irradiation using two types of irradiators (20
and 200 mGy/day). When total dose reached 0.2, 1, 2 and 3Gy, we compared the numbers of HSC and
progenitors in femurs. Results: It is clearly different among investigated blood cells how to response 200
mGy/day-IR. The numbers of HSCs in 200 mGy/day-irradiated mice were increased at day 1 (0.2Gy), and
steeply decreased to similar degree of non-irradiated mice until day 5 (1Gy). The initial transient increases
were also found in common lymphoid progenitors, but not in common myeloid progenitors (CMPs). 200
mGy/day-irradiated CMPs were decreased during irradiation, but recovered after irradiation with showing
overproduction at 50 days after irradiation. In contrast, responses to 20 mGy/day-IR were similar among
HSCs and progenitors, and there were only a little difference in comparison with non-irradiated mice.
Differences by dose rate of IR were found in CMP as significant decreases of CMP numbers in 200
mGy/day-irradiated mice in comparison with those in 20 mGy/day-irradiated mice when total doses were
1, 2 and 3Gy. Conclusion: This study shows that radiation effect on murine hematopoietic cells alters by
dose rate, cell differentiation stage and timing after start of irradiation. This study was performed under
contract with the Aomori Prefectural Government, Japan.
(PS4-05) Cancer cells that survive radiation therapy acquire HIF-1 activity and translocate towards
tumour blood vessels. Minoru Kobayashi; Masahiro Hiraoka; and Hiroshi Harada, Department of
Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine., Kyoto,
Japan
Tumor recurrence frequently occurs after radiotherapy, but the characteristics, intratumoral
localization and post-irradiation behavior of radioresistant cancer cells remain largely unknown. Here we
develop a sophisticated strategy to track the post-irradiation fate of the cells, which exist in perinecrotic
regions at the time of radiation. Although the perinecrotic tumor cells are originally hypoxia-inducible
factor 1 (HIF-1)-negative, they acquire HIF-1 activity after surviving radiation, which triggers their
235 | P a g e
of the irradiated cocultured tumor cells will also be presented. Together, the results show that CAFs
greatly affect the response of tumor cells. Further, the increased oxidative stress initiated by the cancer
cells, and the concomitant increase in antioxidant activity of CAFs, may drive CAFs’ formation and
contribute to their radioresistance through an adaptive response mechanism.
(PS4-04) Dynamics of hematopoietic stem cells and progenitors in C3H mice chronically irradiated at
1
2
2
low dose rate. Part I. Tokuhisa Hirouhi ; Mitsuaki Ojima ; Junya Ishikawa, assistant professor ; Nobuhiko
1
4
2
3
Ban ; Shizue Izumi ; and Michiaki Kai, Institute for Environmental Sciences, Rokkasho, Japan ; Oita
2
3
University of Nursing and Health Sciences, Oita, Japan ; Tokyo Healthcare University, Meguro, Japan ; and
4
Department of Computer Science and Intelligent Systems, Oita University, Oita, Japan
Objective: A dose-rate effect of radiation is important for estimating cancer risk, but a whole
picture of them has not been clarified. High-dose-rate ionizing radiation (IR) develops acute myeloid
leukemia in mice 1-2 years after irradiation. Continuous low-dose-rate IR also causes murine myeloid
leukemia. Chromosomal aberrations of leukemic cell in high- and low-dose-rate IR-induced leukemias are
apparently different. In order to clarify a mechanism causing the chromosomal differences, we
continuously investigated long-lived hematopoietic stem cells (HSCs) and progenitors during and after
irradiation. Methods: C3H mice were subjected to total-body irradiation using two types of irradiators (20
and 200 mGy/day). When total dose reached 0.2, 1, 2 and 3Gy, we compared the numbers of HSC and
progenitors in femurs. Results: It is clearly different among investigated blood cells how to response 200
mGy/day-IR. The numbers of HSCs in 200 mGy/day-irradiated mice were increased at day 1 (0.2Gy), and
steeply decreased to similar degree of non-irradiated mice until day 5 (1Gy). The initial transient increases
were also found in common lymphoid progenitors, but not in common myeloid progenitors (CMPs). 200
mGy/day-irradiated CMPs were decreased during irradiation, but recovered after irradiation with showing
overproduction at 50 days after irradiation. In contrast, responses to 20 mGy/day-IR were similar among
HSCs and progenitors, and there were only a little difference in comparison with non-irradiated mice.
Differences by dose rate of IR were found in CMP as significant decreases of CMP numbers in 200
mGy/day-irradiated mice in comparison with those in 20 mGy/day-irradiated mice when total doses were
1, 2 and 3Gy. Conclusion: This study shows that radiation effect on murine hematopoietic cells alters by
dose rate, cell differentiation stage and timing after start of irradiation. This study was performed under
contract with the Aomori Prefectural Government, Japan.
(PS4-05) Cancer cells that survive radiation therapy acquire HIF-1 activity and translocate towards
tumour blood vessels. Minoru Kobayashi; Masahiro Hiraoka; and Hiroshi Harada, Department of
Radiation Oncology and Image-applied Therapy, Kyoto University Graduate School of Medicine., Kyoto,
Japan
Tumor recurrence frequently occurs after radiotherapy, but the characteristics, intratumoral
localization and post-irradiation behavior of radioresistant cancer cells remain largely unknown. Here we
develop a sophisticated strategy to track the post-irradiation fate of the cells, which exist in perinecrotic
regions at the time of radiation. Although the perinecrotic tumor cells are originally hypoxia-inducible
factor 1 (HIF-1)-negative, they acquire HIF-1 activity after surviving radiation, which triggers their
235 | P a g e
