Apoptosis induced at different dose rates: implication for the shoulder region of cell survival curves

doi:10.1016/0167-8140(94)90099-X

Radiotherapy and Oncology

Volume 32, Issue 2, August 1994, Pages 129-136

https://doi.org/10.1016/0167-8140(94)90099-X Get rights and content

Abstract

Apoptosis is induced by radiation, administered at different dose rates of 3–60 Gy/h, in rat embryo cells transfected with a c-myc oncogene (REC:myc(chl)) or with a c-Ha-ras oncogene (REC:ras(chl)). Apoptosis is evaluated in terms of altered morphology, chromatin condensation and DNA fragmentation. The apoptotic dose response of REC:myc(chl) rises steeply at low doses (to about 40% at 5 Gy), and reaches a plateau at high doses (of about 60% at 15 Gy). In comparison with REC:myc(chI), the REC:ras(chI) is much less susceptible, with a maximum apoptotic fraction of about 10%. Interestingly, radiation-induced apoptosis is nearly dose-rate independent. In parallel, we assessed radiation-induced cell-killing as assayed by colony-formation. In contrast to that observed for apoptosis, the dose response of colony-formation is strongly dependent on dose rate. Cell surviving fraction measured at 3 Gy/h decreases exponentially with dose, with REC:myc(chl) exhibiting a steeper slope than REC:ras(chl). Thus, the different low-dose-rate radiosensitivity of the two cell lines may in part be due to their different susceptibility to radiation-induced apoptosis. Taken together, these findings suggest that radiation-induced apoptosis contributes significantly to the initial (shoulder) region of acute dose-rate survival curves of susceptible cells, and may have implications for fractionated and low dose rate radiotherapy

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Original paperApoptosis induced at different dose rates: implication for the shoulder region of cell survival curves

Abstract

Int. Rev. Exp. Pathol.

Cell

Int. J. Radiat. Oncol., Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phyb.

Constitutive c-myc expression in an IL-3 dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis

Oncogene

Apoptotic cell death induced by c-myc is inhibited by bcl-2

Nature

Transfected c-myc and c-Has-ras modulate radiation-induced apoptosis in rat embryo cells

Radiat. Res.

Thymocyte apoptosis induced by p53-dependent pathways

Nature

IL-2 addiction: withdrawal of growth factor activates a suicide program in dependent T cells

Lymphokine Res.

Rat embryo cells immortalized with transfected oncogenes are transformed by γ-irradiation

Radiat. Res.

Cooperative interaction between c-myc and bcl-2 proto-oncogenes

Nature

Beta-radiation from tracer doses of 32p induces massive apoptosis in a Burkitt's lymphoma cell line

Int. J. Radiat. Biol.

Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics

Br. J. Cancer

Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes

Nature

Interleukin-2 programs mouse T lymphocytes for apoptosis

Nature

Radioresistance induced by oncogenic transformation

Radiat. Res.

p53-dependent apoptosis modulates the cytotoxicity of anticancer agents

Cell

p53 is required for radiation-induced apoptosis in mouse thymocytes

Nature

Inhibitors of protein synthesis and RNA synthesis prevent neuronal death caused by nerve growth factor deprivation

J. Cell Biol.

Increase G2 delay in radiation-resistant cells obtained by transformation of primary rat embryo cells with the encogenes H-ras and v-myc

Radiat. Res.

Heterogeneity in the development of apoptosis in irradiated murine tumors of different histologies

Int. J. Radiat. Biol.

Original paper
Apoptosis induced at different dose rates: implication for the shoulder region of cell survival curves

Beta-radiation from tracer doses of ³²p induces massive apoptosis in a Burkitt's lymphoma cell line

Increase G₂ delay in radiation-resistant cells obtained by transformation of primary rat embryo cells with the encogenes H-ras and v-myc