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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 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.

journal_name

Blood

journal_title

Blood

authors

Haro KJ,Scott AC,Scheinberg DA

doi

10.1182/blood-2012-01-404509

subject

Has Abstract

pub_date

2012-09-06 00:00:00

pages

2087-97

issue

10

eissn

0006-4971

issn

1528-0020

pii

blood-2012-01-404509

journal_volume

120

pub_type

杂志文章

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