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double-negative thymocytes, which are the presumptive initiating cells for radiation-induced T-cell
lymphoma, by flow-cytometry based cell sorting. Then, we examine p53 accumulation, the amount of
Rad51 and DNA-PKcs proteins as well as co-localization of γ-H2AX and Rad51 after irradiation. It is known
that Pten and Ikaros function as suppressors of cell proliferation. Thus, relative amount and role of Pten
and Ikaros in thymic recovery may differ between two age groups.
(PS2-41) Contribution of quantitative trait loci on chromosomes 1, 7 and 9 to radiation-induced
pulmonary fibrosis in mice. Lisa Honeyman; Marie-Eve Bergeron; and Christina K. Haston, McGill
University, Montreal, Canada
Introduction: Previous investigations have shown that there is a strain-dependent difference in
response to thoracic radiation in mice; C57Bl/6J (B6) mice are susceptible to fibrosing alveolitis (fibrosis)
and C3H/HeJ (C3H) mice are resistant. Our laboratory has previously identified quantitative trait loci
(QTLs) which are associated with the development of radiation-induced fibrosis in C57Bl/6J mice.
Approach: In this study, congenic mice with genomic regions from the fibrosis-resistant strain C3H on a
fibrosis-prone B6 background were used to investigate QTLs on chromosomes 1, 7, and 9. Male mice were
exposed to 18Gy whole-thorax irradiation and the phenotypes of survival time, inflammatory cell types,
alveolitis, and fibrosis were assessed and compared to those of B6 mice. Results: Chromosome 1 congenic
mice had a significantly longer post-irradiation survival time and less severe alveolitis and fibrosis than B6
mice. However, the chromosome 1 mice did not differ from B6 in inflammatory cell types present in the
bronchoalveolar lavage. Congenic chromosome 7 and 9 mice had no differences as compared to B6 mice
in the phenotypes of post-irradiation survival time, alveolitis, fibrosis, or inflammatory cell type.
Conclusions: Congenic mice with C3H alleles on chromosome 1 differed in radiation response from B6
mice, suggesting that these genetic regions are involved in the development of fibrosis. The loci on
chromosomes 7 and 9 did not influence the radiation response of congenic mice, indicating that genetic
elements in this region are not sufficient to lead to the development of radiation-induced fibrosis.
(PS2-42) Radiation mitigator drugs jp4-039 and mms350 alter RNA transcription in radiosensitive
fanconi anemia fancd2-/- (fvb/n) bone marrow stromal cells. Ashwin Shinde; Byung Han Rhieu; Michael
W. Epperly; Hong Wang; Donna Shields; Darcy Franicola; Xichen Zhang; Tracy Dixon; Peter Wipf; Melissa
Sprachman; and Joel S. Greenberger, University of Pittsburgh Cancer Institute, Pittsburgh, PA
Purpose: Bone marrow stromal cells derived from Fanconi anemia (FA) mouse long term bone
marrow cultures are radiosensitive compared to those from wild-type littermates. We tested the effects
of the GS-nitroxide, JP4-039, and the water-soluble oxetanyl sulfoxide, MMS350, potent in vivo radiation
mitigators ,(Kalash et al. Rad. Res. 180:474-490, 2013; Berhane et al. Rad. Res. 181:76-89, 2014) on RNA
transcripts in these cells. Methods: Stromal cells derived from long-term bone marrow cultures (LTBMCs)
of Fancd2+/+ and Fancd2-/- mice (FVB/N background) were either drug-treated or untreated and tested
for expression of 14 representative gene transcripts involved in irradiation damage response,
inflammation, stress response, promoter binding, and apoptosis. Treated samples were compared by
Student's t-test to untreated samples within the same genotype. P-values < 0.05 were considered
significant. Results: In Fancd2-/- and wild-type Fancd2+/+ cells, JP4-039 and MMS350 suppressed IL-1A
(≤ -48%) and Rad51 (≤ -35%), and induced TLR4 (≥ 26%) (p ≤ 0.038 for all groups) In Fancd2-/- cells, JP4-
157 | P a g e
lymphoma, by flow-cytometry based cell sorting. Then, we examine p53 accumulation, the amount of
Rad51 and DNA-PKcs proteins as well as co-localization of γ-H2AX and Rad51 after irradiation. It is known
that Pten and Ikaros function as suppressors of cell proliferation. Thus, relative amount and role of Pten
and Ikaros in thymic recovery may differ between two age groups.
(PS2-41) Contribution of quantitative trait loci on chromosomes 1, 7 and 9 to radiation-induced
pulmonary fibrosis in mice. Lisa Honeyman; Marie-Eve Bergeron; and Christina K. Haston, McGill
University, Montreal, Canada
Introduction: Previous investigations have shown that there is a strain-dependent difference in
response to thoracic radiation in mice; C57Bl/6J (B6) mice are susceptible to fibrosing alveolitis (fibrosis)
and C3H/HeJ (C3H) mice are resistant. Our laboratory has previously identified quantitative trait loci
(QTLs) which are associated with the development of radiation-induced fibrosis in C57Bl/6J mice.
Approach: In this study, congenic mice with genomic regions from the fibrosis-resistant strain C3H on a
fibrosis-prone B6 background were used to investigate QTLs on chromosomes 1, 7, and 9. Male mice were
exposed to 18Gy whole-thorax irradiation and the phenotypes of survival time, inflammatory cell types,
alveolitis, and fibrosis were assessed and compared to those of B6 mice. Results: Chromosome 1 congenic
mice had a significantly longer post-irradiation survival time and less severe alveolitis and fibrosis than B6
mice. However, the chromosome 1 mice did not differ from B6 in inflammatory cell types present in the
bronchoalveolar lavage. Congenic chromosome 7 and 9 mice had no differences as compared to B6 mice
in the phenotypes of post-irradiation survival time, alveolitis, fibrosis, or inflammatory cell type.
Conclusions: Congenic mice with C3H alleles on chromosome 1 differed in radiation response from B6
mice, suggesting that these genetic regions are involved in the development of fibrosis. The loci on
chromosomes 7 and 9 did not influence the radiation response of congenic mice, indicating that genetic
elements in this region are not sufficient to lead to the development of radiation-induced fibrosis.
(PS2-42) Radiation mitigator drugs jp4-039 and mms350 alter RNA transcription in radiosensitive
fanconi anemia fancd2-/- (fvb/n) bone marrow stromal cells. Ashwin Shinde; Byung Han Rhieu; Michael
W. Epperly; Hong Wang; Donna Shields; Darcy Franicola; Xichen Zhang; Tracy Dixon; Peter Wipf; Melissa
Sprachman; and Joel S. Greenberger, University of Pittsburgh Cancer Institute, Pittsburgh, PA
Purpose: Bone marrow stromal cells derived from Fanconi anemia (FA) mouse long term bone
marrow cultures are radiosensitive compared to those from wild-type littermates. We tested the effects
of the GS-nitroxide, JP4-039, and the water-soluble oxetanyl sulfoxide, MMS350, potent in vivo radiation
mitigators ,(Kalash et al. Rad. Res. 180:474-490, 2013; Berhane et al. Rad. Res. 181:76-89, 2014) on RNA
transcripts in these cells. Methods: Stromal cells derived from long-term bone marrow cultures (LTBMCs)
of Fancd2+/+ and Fancd2-/- mice (FVB/N background) were either drug-treated or untreated and tested
for expression of 14 representative gene transcripts involved in irradiation damage response,
inflammation, stress response, promoter binding, and apoptosis. Treated samples were compared by
Student's t-test to untreated samples within the same genotype. P-values < 0.05 were considered
significant. Results: In Fancd2-/- and wild-type Fancd2+/+ cells, JP4-039 and MMS350 suppressed IL-1A
(≤ -48%) and Rad51 (≤ -35%), and induced TLR4 (≥ 26%) (p ≤ 0.038 for all groups) In Fancd2-/- cells, JP4-
157 | P a g e
