Effects of Low-Dose Neutrons Applied at Reduced Dose Rate on Human Melanoma Cells

Dionet, C; Tchirkov, Andréï; Alard, Jean Pierre; Arnold, Jack; Dhermain, J.; Rapp, Maryse; Bodez, V.; Tamain, J. C.; Monbel, Isabelle; Malet, P; Kwiatkowski, Fabrice; Donnarieix, D.; Veyre, A.; Verrelle, Pierre

doi:10.1667/0033-7587(2000)154[0406:eoldna]2.0.co;2

Cited by 27 publications

(13 citation statements)

References 17 publications

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“…Inverse dose-rate effects have been shown for the human cervical carcinoma cell line NHIK 3025 15 and for the human melanoma cell line M4 Beu. 16 Thus, whether cells show a direct or inverse dose-rate effect seems to depend on cell-type and probably also on radiation quality (e.g., the dose-rate range studied and the LET). The long accumulation time for a certain dose when given at low doserate has actually been assumed to be the cause of the direct dose-rate effect.…”

Section: Discussionmentioning

confidence: 99%

Early Effects of Low Dose-Rate Radiation on Cultured Tumor Cells

Carlsson

Håkansson²,

Eriksson³

et al. 2003

Cancer Biotherapy and Radiopharmaceuticals

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Low-dose hyperradiosensitivity (HRS) has been found for several cell types after exposure to low doses, < 0.5 Gy, of high dose-rate (typically 50-150 Gy/h) low-LET radiation. HRS precedes the occurrence of a relative resistance for doses above 0.5-1 Gy. A critical question is whether HRS is of importance in radionuclide therapy where the dose-rate is low but the total dose might be high. An indication that cells exposed to low dose-rate can be kept hyperradiosensitive has recently been published. We have in the present study applied cells without (glioma U373MG) and with (glioma U118MG and colon carcinoma HT29) HRS and studied early effects, up to one week, during low dose-rate (LDR), 0.05-0.09 Gy/hours, exposure (total dose after one week: 11.8 +/- 1.5 Gy). The cells were grown on thin foils above a (32)P source placed in a cell culture chamber. Cell number reductions, cell-cycle disturbances, and changed numbers of apoptotic cells were analyzed after continuous LDR exposures. There seemed to be no relation with HRS when the cell number reduction was considered. The U373MG cells, lacking HRS, had the strongest cell number reduction due to a combination of a G(2) block and increased apoptosis. The U118MG and HT29 cells, both having HRS, had surprisingly low cell number reductions. U118MG had only a G(2) block but no increase in apoptosis. HT29 had both a G(2) block and an increase in apoptosis but the apoptosis change was somewhat smaller than for U373MG. Thus, there seemed to be no obvious relation between HRS and early cellular effects when the cells were analyzed after continuous LDR exposure.

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Section: Discussionmentioning

confidence: 99%

Early Effects of Low Dose-Rate Radiation on Cultured Tumor Cells

Carlsson

Håkansson²,

Eriksson³

et al. 2003

Cancer Biotherapy and Radiopharmaceuticals

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“…HRS has also been found in M4Be melanoma cells using neutrons. 29 Moreover, 2 radiosensitive tumor cell lines, H460 and MCF7, failed to display HRS. These data suggest that HRS may be an intrinsic characteristic of human radioresistant tumors and of at least some normal human cells.…”

Section: Etoposide Sensitizes Malignant Glioma Cells At Low Radiationmentioning

confidence: 99%

Human malignant glioma cell lines are sensitive to low radiation doses

Beauchesne

Bertrand

et al. 2003

Intl Journal of Cancer

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Malignant gliomas display aggressive local behavior and are not cured by existing therapy. Some cell lines that are considered radioresistant respond to low radiation doses (<1 Gy) with increased cell killing (low-dose hypersensitivity). In our study, 4 of 5 human glioma cell lines exhibited significant X-ray sensitivity at doses below 1 Gy. The surviving fractions (SFs) obtained at 0.7 and/or 0.8 Gy were comparable to those at 1.5 Gy. Low-dose hypersensitivity was evident when irradiation was combined with etoposide treatment. Repeated irradiation with low doses was markedly more effective than irradiation with single, biologically equivalent doses in decreasing SFs, inhibiting xenograft tumor growth in mice. All experiments were conducted with an accelerator used in clinics, establishing that low-dose hypersensitivity was present following megavoltage X-irradiation. Malignant glioma is one of the most radioresistant tumor types and accounts for approximately 60% of all primary brain tumors in adults. The prognosis of malignant glioma patients remains dismal. The standard of care has been essentially unchanged for many decades: surgical resection of as much of the tumor as is safe, followed by radiation therapy and chemotherapy. Even under the best of circumstances, in which essentially all of the tumor seen on magnetic resonance imaging scan can be surgically removed and the patients fully treated with radiation and chemotherapy, mean survival is extended only from 2-3 months to 1 year. [1][2][3] Despite the widespread use of radiation therapy for the treatment of malignant glioma, the uniformly poor response of these tumors remains a critical problem in the management of these patients. 3 Disruption of cell-cycle arrest or apoptotic pathways by INK4a loss or by p53 mutations or inactivation (approx. 40 -60% of malignant gliomas have p53 mutations) associated with CDK4 amplification or Rb loss may be significant factors in determining the response of these tumors to irradiation and treatment outcome. 4 -6 The radiation survival response of mammalian cells is more complicated than once believed. A few studies indicate that some human cell lines are sensitive to killing by low radiation doses (Ͻ1 Gy). This has been termed low-dose hyper-radiosensitivity (HRS). [7][8][9][10][11] This may reflect differential triggering or induction of repair mechanisms. Cells may be sensitive to low doses because repair mechanisms are not induced, whereas higher doses may cause enough damage to induce or trigger repair mechanisms and, therefore, exhibit increased radioresistance. 9 We report here that 4 malignant glioma cell lines displayed a significant increase in X-ray radiosensitivity at doses below 1 Gy compared to the prediction extrapolated from a linear-quadratic (LQ) model that fits to the data at higher doses. In addition, this phenomenon was extended to 4 human melanoma cell lines and MRC5 human fibroblasts. Moreover, ultrafractionated irradiation with low doses was markedly more effective than conventional irradiati...

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“…In human melanoma cells, exposure to fast 14 MeV neutrons induces a hyperradiosensitivity (HRS) at a very low dose of 50 milliGrays (mGy) when delivered at a very low dose rate (VLDR) of 0.8 mGy/min (Dionet et al 2000). At doses between 100 mGy and 350 mGy HRS is followed by increased cell survival.…”

Section: Introductionmentioning

confidence: 99%

Different dose rate-dependent responses of human melanoma cells and fibroblasts to low dose fast neutrons

Dionet

Müller-Barthélémy

Marceau

et al. 2016

International Journal of Radiation Biology

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Melanoma cells or fibroblasts exert their own survival behaviour at very low doses of neutrons, suggesting that in some cases there is a differential between cancer and normal cells radiation responses. Only the survival of fibroblasts at HDR fits the linear no-threshold model. This new insight into human cell responses to very low doses of neutrons, concerns natural radiations, surroundings of accelerators, proton-therapy devices, flights at high altitude. Furthermore, ATP inhibitors could increase HRS during high-linear energy transfer (high-LET) irradiation.

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Effects of Low-Dose Neutrons Applied at Reduced Dose Rate on Human Melanoma Cells

Cited by 27 publications

References 17 publications

Early Effects of Low Dose-Rate Radiation on Cultured Tumor Cells

Early Effects of Low Dose-Rate Radiation on Cultured Tumor Cells

Human malignant glioma cell lines are sensitive to low radiation doses

Different dose rate-dependent responses of human melanoma cells and fibroblasts to low dose fast neutrons

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