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Int J Radiat Oncol Biol Phys. 2006 Jul 1;65(3):859-66.

Histone deacetylase inhibitors enhance phosphorylation of histone H2AX after ionizing radiation.

Author information

1
Division of Molecular Oncology and Molecular Diagnosis, Graduate School of Medicine, Sapporo Medical University, Sapporo, Hokkaido, Japan.

Abstract

PURPOSE:

Histone deacetylase (HDAC) inhibitors are believed to be promising radiosensitizers. To explore their effects on ionizing radiation (IR), we examined whether the HDAC inhibitors m-carboxycinnamic acid bis-hydroxamide (CBHA) and depsipeptide FK228 affect H2AX phosphorylation (gamma-H2AX), a landmark of DNA double-strand breaks after IR exposure.

METHODS AND MATERIALS:

We evaluated the effects of the HDAC inhibitors on clonogenic assay in human lung carcinoma A549 cells and progression of A549 xenograft tumors. IR-induced DNA damage was evaluated by histone gamma-H2AX. Histone hyperacetylation was induced by overexpression of histone acetyltransferase p300 and evaluated by Western blots.

RESULTS:

M-carboxycinnamic acid bishydroxyamide pretreatment radiosensitized A549 cells and strongly inhibited A549 xenograft tumor progression. CBHA and FK228, but not 5-fluorouracil, enhanced IR-induced gamma-H2AX in A549 and other cancer cell lines. Overexpression of p300 similarly augmented IR-induced gamma-H2AX.

CONCLUSION:

The results of this study suggest that HDAC inhibitors enhance IR-induced gamma-H2AX, most likely through histone hyperacetylation, and radiosensitize various cancers.

PMID:
16751067
DOI:
10.1016/j.ijrobp.2006.03.019
[Indexed for MEDLINE]

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