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Abstract 426: In-field head and neck irradiation radiosensitivity of FancD2-/- mice and bystander effect reduction of distant bone marrow hematopoietic progenitor cells
Background: Irradiation induced normal tissue toxicity limits effective radiotherapy of individuals with DNA repair defects including Fanconi anemia. We quantitated in-field head and neck tissue response in irradiated Fanconi anemia knockout mice, FancD2-/-, compared to wild type, FancD2+/+ & he...
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Published in: | Cancer research (Chicago, Ill.) Ill.), 2013-04, Vol.73 (8_Supplement), p.426-426 |
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Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | Background: Irradiation induced normal tissue toxicity limits effective radiotherapy of individuals with DNA repair defects including Fanconi anemia. We quantitated in-field head and neck tissue response in irradiated Fanconi anemia knockout mice, FancD2-/-, compared to wild type, FancD2+/+ & heterozygous FancD2+/- mice. We also assessed bystander effect of head and neck irradiation on distant bone marrow hematopoietic progenitor cell numbers.
Method: Adult 10-12wk old FevB background FancD2+/+, +/- and -/- mice were irradiated to the head & neck to 24Gy, 26Gy, 28Gy or 30Gy (n=3) shielding all tissue below the cervical spine. On day 2 or 5 post irradiation, mice were sacrificed and tongue tissue and one femur excised for histopathology. Bone marrow of the contralateral femur was plated for colony assay. Colony forming unit-granulocyte macrophage (CFU-GM), burst forming unit erythroid (BFU-E), and colony forming unit-granulocyte-erythroid-megakaryocyte-monocyte (CFU-GEMM) numbers were counted & each genotype compared to its unirradiated control. H&E stained tongue sections were scored for oral mucositis.
Results: Both FancD2-/- & FancD2+/- mice were radiosensitive to lower doses compared to FancD2+/+ mice measured as percent ulceration of the squamous layer of tongue epithelium 5 days post irradiation. Both FancD2+/- and FancD2-/- mice had significantly higher ulceration after 26Gy (52.8±6.5%, p=0.0014 and and 59.4±3.4%, p=0.0001, respectively) compared to wild type FancD2+/+ (21.7±4.7%). At the lower dose of 24Gy, FancD2+/- and -/- had higher percent ulceration (p=0.0001 and p=0.0003) than FancD2+/+ mice irradiated to even higher doses of 26Gy and 28Gy. FancD2+/+ mice had high levels of ulceration after 28Gy (p=0.2355). While there was no difference in distant bone marrow cellularity between irradiated groups, both FancD2-/- & FancD2+/- showed bystander reduction in colony forming cells. CFU-GM were significantly reduced at 2 days after 26Gy in FancD2+/- mice compared to unirradiated controls (p=0.007). FancD2 -/- mice had decreased BFU-E after 24Gy (p=0.009) & CFU-GEMM after 26Gy (p=0.048) and reduced BFU-E numbers after 26Gy (p=0.031). FancD2-/- mice had significantly less CFU-GM after either 26Gy or 28Gy (p=0.017 and p=0.028, respectively). FancD2-/- & +/- mice, at 5 days after 26Gy, had less CFU-GM (p=0.001 and 0.012, respectively) and CFU-GEMM (p=0.014 and p=0.004, respectively) compared to unirradiated controls. There was no reduction in CFU-GM, BFU- |
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ISSN: | 0008-5472 1538-7445 |
DOI: | 10.1158/1538-7445.AM2013-426 |