Changes in Radiosensitivity and Dispersion of Chromatin during the Cell Cycle of Synchronous Chinese Hamster Cells

Dewey, William C.; Noel, Jack; Dettor, C. M.

doi:10.2307/3573575

Cited by 105 publications

(22 citation statements)

References 47 publications

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“…The initial idea for HDI as a radiosensitizer is that the blockage of HDAC activity by HDI drugs promotes hyperacetylation in core histones and leads to a more relaxed chromatin structure 12,13 ; DNA in decondensed chromatin is relatively sensitive to DNA damage induced by IR. 14,15 This model is supported by recent studies that have demonstrated that HDI, such as trichostatin A (TSA), sodium butyrate (NaB), FK228, and MS-275, enhance radiation-induced cell death and increase IR-induced DNA DSBs in a variety of cancer cells. [16][17][18][19] However, details of molecular mechanisms mediating radiosensitization by HDI are, at present, not clear.…”

Section: Introductionsupporting

confidence: 52%

HDAC Inhibitor, Valproic Acid, Induces p53-Dependent Radiosensitization of Colon Cancer Cells

Chen

Wong

Radany

et al. 2009

Cancer Biotherapy and Radiopharmaceuticals

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Agents that inhibit histone deacetylases (HDAC inhibitors) have been shown to enhance radiation response. The aim of this study was to evaluate the effects of low, minimally cytotoxic concentrations of the HDAC inhibitor, valproic acid (VPA), on radiation response of colorectal cancer cells. Cell lines LS174T and an isogenic pair of HCT116, which differed only for the presence of wild-type p53, were exposed to ionizing radiation (IR) alone, VPA alone, or the combination. Clonogenic survival, g-H2AX induction, apoptosis, changes in mitochondrial membrane potential, and mitochondrial levels of p53 and Bcl-2 family proteins were assessed. In vivo studies monitored tumor growth suppression after therapy in mice bearing HCT116=p53 þ=þ and HCT116=p53 À=À tumor xenografts. VPA led to radiosensitization, which was dependent on p53 status. A decrease in clonogenic survival, an increase in apoptosis, and an increase in levels of g-H2AX were observed after VPAþIR, compared to IR alone, in wild-type p53 cells (LS174T and HCT116=p53 þ=þ ), as opposed to p53 null cells (HCT116=p53 À=À). Exposure to VPA resulted in enhancement of IR-induced mitochondrial localizations of Bax and Bcl-xL, mitochondrial membrane potential, and cytochrome c release only in wild-type p53 cell lines. VPA also enhanced tumor growth suppression after IR only in wild-type p53 xenografts. These data suggest that VPA may have an important role in enhancing radiotherapy response in colorectal cancer, particularly in tumors with the wildtype p53 genotype.

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Section: Introductionsupporting

confidence: 52%

HDAC Inhibitor, Valproic Acid, Induces p53-Dependent Radiosensitization of Colon Cancer Cells

Chen

Wong

Radany

et al. 2009

Cancer Biotherapy and Radiopharmaceuticals

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“…(25), (29), and (30) are, as seen in Fig. 4, similar in that the majority of the potential reaction partners lie at an intermediate distance from a sublesion.…”

Section: Short Range Interactionmentioning

confidence: 50%

“…The possibility of dual action in its usual interpretation has therefore been excluded, and it has also been stated that the alternative treatment in terms of the distance model will not overcome all of the difficulties (28). As seen from the example in It should be noted that the evidence provided by electron microscopy (29) does in fact indicate that DNA is arranged in clusters during interphase.…”

Section: Short Range Interactionmentioning

confidence: 77%

A Generalized Formulation of Dual Radiation Action

Hobbs¹

1978

Radiation Research

418

246

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“…Cells in G2/M phase are particularly vulnerable to radiation exposure, while cells in S phase are markedly more resistant. Cells arrested at the G1/S checkpoint display greater sensitivity than in the rest of G1 (Dewey et al, 1971(Dewey et al, , 1972. These differences in radiosensitivity are large.…”

Section: Cell Cyclementioning

confidence: 94%