Mechanisms of resistance to high and low linear energy transfer radiation in myeloid leukemia cells
| Autor: | Andrew C. Scott, David A. Scheinberg, Kurtis J. Haro |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Genome instability
DNA Repair DNA repair DNA damage Cell Survival medicine.medical_treatment Immunology Apoptosis HL-60 Cells Biology Biochemistry Radioresistance medicine Humans DNA Breaks Double-Stranded Linear Energy Transfer RNA Small Interfering Myeloid Neoplasia Myeloid leukemia Dose-Response Relationship Radiation Cell Biology Hematology medicine.disease Alpha Particles Clone Cells G2 Phase Cell Cycle Checkpoints Leukemia Haematopoiesis Gamma Rays Radioimmunotherapy Cancer research Rad51 Recombinase |
| Popis: | Low linear energy transfer (LET) ionizing radiation (IR) is an important form of therapy for acute leukemias administered externally or as radioimmunotherapy. IR is also a potential source of DNA damage. High LET IR produces structurally different forms of DNA damage and has emerged as potential treatment of metastatic and hematopoietic malignancies. Therefore, understanding mechanisms of resistance is valuable. We created stable myeloid leukemia HL60 cell clones radioresistant to either γ-rays or α-particles to understand possible mechanisms in radioresistance. Cross-resistance to each type of IR was observed, but resistance to clustered, complex α-particle damage was substantially lower than to equivalent doses of γ-rays. The resistant phenotype was driven by changes in: apoptosis; late G2/M checkpoint accumulation that was indicative of increased genomic instability; stronger dependence on homology-directed repair; and more robust repair of DNA double-strand breaks and sublethal-type damage induced by γ-rays, but not by α-particles. The more potent cytotoxicity of α-particles warrants their continued investigation as therapies for leukemia and other cancers. |
| Databáze: | OpenAIRE |
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