Mechanisms of resistance to high and low linear energy transfer radiation in myeloid leukemia cells Journal Article

Authors: Haro, K. J.; Scott, A. C.; Scheinberg, D. A.
Article Title: Mechanisms of resistance to high and low linear energy transfer radiation in myeloid leukemia cells
Abstract: 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 G 2/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. © 2012 by The American Society of Hematology.
Keywords: controlled study; human cell; radiation dose; phenotype; dna damage; cell survival; dna repair; apoptosis; rna, small interfering; cytotoxicity; dose-response relationship, radiation; genomic instability; leukemia cell; energy transfer; dna breaks, double-stranded; radiosensitivity; cell clone; sequence homology; low energy radiation; clone cells; cross resistance; rad51 recombinase; myeloid leukemia; alpha radiation; gamma radiation; gamma rays; alpha particles; linear energy transfer; hl-60 cells; cell strain hl 60; g2 phase cell cycle checkpoints; g2 phase cell cycle checkpoint; m phase cell cycle checkpoint
Journal Title: Blood
Volume: 120
Issue: 10
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2012-09-06
Start Page: 2087
End Page: 2097
Language: English
DOI: 10.1182/blood-2012-01-404509
PROVIDER: scopus
PMCID: PMC3437596
PUBMED: 22829630
Notes: --- - "Export Date: 1 October 2012" - "CODEN: BLOOA" - "Source: Scopus"
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MSK Authors
  1. Kurtis Haro
    5 Haro
  2. Andrew Crosbie Scott
    13 Scott