Page 155 - 2014 Printable Abstract Book
P. 155
(PS2-34) Characterization of the tumor spectrum arising in HZE ion irradiated outbred mice. Elijah F.
Edmondson, DVM; Debra Kamstock, DVM, PhD, DACVP; Christina Fallgren; and Mike Weil, PhD, Colorado
State University, Fort Collins, CO
Space travel exposes astronauts to unique forms of densely ionizing radiation known as high
charge and energy (HZE) ions. HZE ions are a constituent of galactic cosmic rays that permeate
interplanetary space and have a high linear energy transfer in comparison to gamma rays. Ionizing
radiation is efficient at causing DNA damage and neoplasia, however, the differential ability of HZE ions
to produce neoplasia and metastatic disease in mammals is largely uncharacterized. Inbred, genetically
identical mice are not ideal for this type of study as differences in tumorigenesis for inbred mice reflect
strain susceptibilities to specific tumor types rather than radiation qualities. Furthermore, heterogeneous
mice are more similar to the heterogeneity of human populations. In the present study, HS/Npt outbred
mice were reverse engineered through breeding of eight well characterized progenitor strains for 70
generations. These outbred mice were exposed to 28Si (n = 300), 56Fe (n = 300), 137Cs gamma rays (n =
600) or sham irradiation (n = 600) and housed for 800 days. Thorough necropsy examinations were
performed on each mouse and all organ systems, including the central nervous system, with an emphasis
on detection of neoplasia. Each tumor was analyzed histologically. For lymphoid neoplasms and
nonlymphoid round cell neoplasms, peripheral blood and bone marrow tissue were analyzed to reveal
leukemic phases. In addition, lymphomas were immunophenotyped using tissue microarrays and
immunohistochemistry for CD45R and CD3. For solid tumors such as harderian gland adenocarcinomas
and hepatocellular carcinomas, all lung fields were examined histologically to detect potential pulmonary
micrometastases. Overall, mice exposed to 3 Gy of gamma irradiation had decreased survival compared
to mice exposed to 0.4 Gy iron or silicon nuclei. Irradiated mice, regardless of the quality of radiation, had
decreased median survival compared to unirradiated controls. Differences in tumor incidences between
radiation groups are pending analysis and will be discussed.
1;2
(PS2-35) HPRT mutant induction in V79 cells at different times after heavy ion irradiation. Pavel Bláha ;
1
1
1
1
1
Igor V. Koshlan ; Natalia A. Koshlan ; Raisa D. Govorun ; Daria V. Elsha ; Anastasia N. Torubarova ; and
2
1
Evgeny A. Krasavin, JINR, Dubna, Russian Federation and FNSPE, CTU in Prague, Prague, Czech Republic
1
Mutation induction in the HPRT gene of the V79 Chinese hamster cells has been observed after
exposure to three types of accelerated ions: O-18, Ne-20, and B-11. Four different irradiation conditions
were used with the linear energy transfer (LET) values in the range of 50 − 153 keV/µm. The dependence
of the mutant fraction on expression time (the incubation period of the cells from irradiation until
reseeding on a selective medium containing 6-thioguanine) was measured for the doses of 0.5, 1, and 2
Gy. The dependance non-linear progression was observed under all irradiation conditions. The mutant
fraction was increasing with expression time; reaching maximum; and falling back to the initial levels. It
was found that after approximately 35 - 45 days (70 - 90 cell generations) the mutant fraction returned to
the levels typical for spontaneous mutants. The mutant fraction reached its maximum in different
expression times under various irradiation conditions. The position of this peak was moving with the LET
value of the used radiation. With increasing LET, the maximum shifted towards longer expression times.
For example, the mutant fraction maximum was observed 7-14 days after O-18 irradiation with LET ~ 116
keV/µm; however, Ne-20 irradiation with LET ~ 153 keV/µm caused the peak to shift to 20 - 26 days after
153 | P a g e
Edmondson, DVM; Debra Kamstock, DVM, PhD, DACVP; Christina Fallgren; and Mike Weil, PhD, Colorado
State University, Fort Collins, CO
Space travel exposes astronauts to unique forms of densely ionizing radiation known as high
charge and energy (HZE) ions. HZE ions are a constituent of galactic cosmic rays that permeate
interplanetary space and have a high linear energy transfer in comparison to gamma rays. Ionizing
radiation is efficient at causing DNA damage and neoplasia, however, the differential ability of HZE ions
to produce neoplasia and metastatic disease in mammals is largely uncharacterized. Inbred, genetically
identical mice are not ideal for this type of study as differences in tumorigenesis for inbred mice reflect
strain susceptibilities to specific tumor types rather than radiation qualities. Furthermore, heterogeneous
mice are more similar to the heterogeneity of human populations. In the present study, HS/Npt outbred
mice were reverse engineered through breeding of eight well characterized progenitor strains for 70
generations. These outbred mice were exposed to 28Si (n = 300), 56Fe (n = 300), 137Cs gamma rays (n =
600) or sham irradiation (n = 600) and housed for 800 days. Thorough necropsy examinations were
performed on each mouse and all organ systems, including the central nervous system, with an emphasis
on detection of neoplasia. Each tumor was analyzed histologically. For lymphoid neoplasms and
nonlymphoid round cell neoplasms, peripheral blood and bone marrow tissue were analyzed to reveal
leukemic phases. In addition, lymphomas were immunophenotyped using tissue microarrays and
immunohistochemistry for CD45R and CD3. For solid tumors such as harderian gland adenocarcinomas
and hepatocellular carcinomas, all lung fields were examined histologically to detect potential pulmonary
micrometastases. Overall, mice exposed to 3 Gy of gamma irradiation had decreased survival compared
to mice exposed to 0.4 Gy iron or silicon nuclei. Irradiated mice, regardless of the quality of radiation, had
decreased median survival compared to unirradiated controls. Differences in tumor incidences between
radiation groups are pending analysis and will be discussed.
1;2
(PS2-35) HPRT mutant induction in V79 cells at different times after heavy ion irradiation. Pavel Bláha ;
1
1
1
1
1
Igor V. Koshlan ; Natalia A. Koshlan ; Raisa D. Govorun ; Daria V. Elsha ; Anastasia N. Torubarova ; and
2
1
Evgeny A. Krasavin, JINR, Dubna, Russian Federation and FNSPE, CTU in Prague, Prague, Czech Republic
1
Mutation induction in the HPRT gene of the V79 Chinese hamster cells has been observed after
exposure to three types of accelerated ions: O-18, Ne-20, and B-11. Four different irradiation conditions
were used with the linear energy transfer (LET) values in the range of 50 − 153 keV/µm. The dependence
of the mutant fraction on expression time (the incubation period of the cells from irradiation until
reseeding on a selective medium containing 6-thioguanine) was measured for the doses of 0.5, 1, and 2
Gy. The dependance non-linear progression was observed under all irradiation conditions. The mutant
fraction was increasing with expression time; reaching maximum; and falling back to the initial levels. It
was found that after approximately 35 - 45 days (70 - 90 cell generations) the mutant fraction returned to
the levels typical for spontaneous mutants. The mutant fraction reached its maximum in different
expression times under various irradiation conditions. The position of this peak was moving with the LET
value of the used radiation. With increasing LET, the maximum shifted towards longer expression times.
For example, the mutant fraction maximum was observed 7-14 days after O-18 irradiation with LET ~ 116
keV/µm; however, Ne-20 irradiation with LET ~ 153 keV/µm caused the peak to shift to 20 - 26 days after
153 | P a g e
