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

Dionet, C; Müller-Barthélémy, Mélanie; Marceau, Geoffroy; Denis, Jean‐Marc; Averbeck, D.; Gueulette, John; Sapin, Vincent; Pereira, Bruno; Tchirkov, Andréï; Chautard, Emmanuel; Verrelle, Pierre

doi:10.1080/09553002.2016.1186300

Cited by 7 publications

(10 citation statements)

References 24 publications

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“…Present data showed alterations in the sphere formation ability, which were more evident following monoenergetic neutron irradiation and following the exposure to the mixed gamma - secondary neutron field, compared to X-rays and medium-energy neutrons (< E n > = 5.8 MeV). Like Dionet et al, who investigated fast neutrons on normal skin fibroblast by cell survival assay, we could show a stronger effect following HDR neutrons compared to LDR neutrons [ 38 ]. In general, most publications concerning sphere formation combining mammary cells and radiation are dealing with cancer cell lines [ 39 , 40 ].…”

Section: Discussionsupporting

confidence: 56%

Comparative study of the effects of different radiation qualities on normal human breast cells

et al. 2017

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BackgroundAs there is a growing number of long-term cancer survivors, the incidence of carcinogenesis as a late effect of radiotherapy is getting more and more into the focus. The risk for the development of secondary malignant neoplasms might be significantly increased due to exposure of healthy tissue outside of the target field to secondary neutrons, in particular in proton therapy. Thus far, the radiobiological effects of these neutrons and a comparison with photons on normal breast cells have not been sufficiently characterised.MethodsMCF10A cells were irradiated with doses of up to 2 Gy with neutrons of different energy spectra and X-rays for comparison. The biological effects of neutrons with a broad energy distribution ( = 5.8 MeV), monoenergetic neutrons (1.2 MeV, 0.56 MeV) and of the mixed field of gamma’s and secondary neutrons ( = 70.5 MeV) produced by 190 MeV protons impinging on a water phantom, were analysed. The clonogenic survival and the DNA repair capacity were determined and values of relative biological effectiveness were compared. Furthermore, the influence of radiation on the sphere formation was observed to examine the radiation response of the potential fraction of stem like cells within the MCF10A cell population.ResultsX-rays and neutrons caused dose-dependent decreases of survival fractions after irradiations with up to 2 Gy. Monoenergetic neutrons with an energy of 0.56 MeV had a higher effectiveness on the survival fraction with respect to neutrons with higher energies and to the mixed gamma - secondary neutron field induced by proton interactions in water. Similar effects were observed for the DNA repair capacity after exposure to ionising radiation (IR). Both experimental endpoints provided comparable values of the relative biological effectiveness. Significant changes in the sphere formation were notable following the various radiation qualities.ConclusionThe present study compared the radiation response of MCF10A cells after IR with neutrons and photons. For the first time it was shown that monoenergetic neutrons with energies around 1 MeV have stronger radiobiological effects on normal human breast cells with respect to X rays, to neutrons with a broad energy distribution ( = 5.8 MeV), and to the mixed gamma - secondary neutron field given by interactions of 190 MeV protons in water. The results of the present study are highly relevant for further investigations of radiation-induced carcinogenesis and are very important in perspective for a better risk assessment after secondary neutron exposure in the field of conventional and proton radiotherapy.Electronic supplementary materialThe online version of this article (10.1186/s13014-017-0895-8) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 56%

Comparative study of the effects of different radiation qualities on normal human breast cells

et al. 2017

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“…DMXL2 is involved in the regulation of the NOTCH signalling pathway in mammalian cells (70), through V-ATPase complex-driven acidification of endocytic compartments (70,71). A global decrease in ATP levels was observed in human fibroblasts exposed to low doses delivered at intermediate dose rates, while the same dose delivered acutely, lead to an increase in ATP, hypothesized to drive survival differences (72). This would be in line with others, who propose the ADP:ATP ratio as an indicator of cell viability, necrosis and apoptosis (73).…”

Section: Discussionmentioning

confidence: 99%

Short- and long-term effects of radiation exposure at low dose and low dose rate in normal human VH10 fibroblasts

Akuwudike,

López-Riego,

Marczyk

et al. 2023

Front. Public Health

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IntroductionExperimental studies complement epidemiological data on the biological effects of low doses and dose rates of ionizing radiation and help in determining the dose and dose rate effectiveness factor.MethodsHuman VH10 skin fibroblasts exposed to 25, 50, and 100 mGy of 137Cs gamma radiation at 1.6, 8, 12 mGy/h, and at a high dose rate of 23.4 Gy/h, were analyzed for radiation-induced short- and long-term effects. Two sample cohorts, i.e., discovery (n = 30) and validation (n = 12), were subjected to RNA sequencing. The pool of the results from those six experiments with shared conditions (1.6 mGy/h; 24 h), together with an earlier time point (0 h), constituted a third cohort (n = 12).ResultsThe 100 mGy-exposed cells at all abovementioned dose rates, harvested at 0/24 h and 21 days after exposure, showed no strong gene expression changes. DMXL2, involved in the regulation of the NOTCH signaling pathway, presented a consistent upregulation among both the discovery and validation cohorts, and was validated by qPCR. Gene set enrichment analysis revealed that the NOTCH pathway was upregulated in the pooled cohort (p = 0.76, normalized enrichment score (NES) = 0.86). Apart from upregulated apical junction and downregulated DNA repair, few pathways were consistently changed across exposed cohorts. Concurringly, cell viability assays, performed 1, 3, and 6 days post irradiation, and colony forming assay, seeded just after exposure, did not reveal any statistically significant early effects on cell growth or survival patterns. Tendencies of increased viability (day 6) and reduced colony size (day 21) were observed at 12 mGy/h and 23.4 Gy/min. Furthermore, no long-term changes were observed in cell growth curves generated up to 70 days after exposure.DiscussionIn conclusion, low doses of gamma radiation given at low dose rates had no strong cytotoxic effects on radioresistant VH10 cells.

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“…It is known that the radiobiological effects of radiation doses depends on factors such as cell type and dose rate( 25 26 ). The radioresistance of lymphocyte cells was examined with a dose rate 1.6 Gy/min and for total doses of 2 to 6 Gy.…”

Section: Discussionmentioning

confidence: 99%

Radioprotective effects of lentil sprouts against X-ray radiation

et al. 2017

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The present study investigated the radioprotective efficacy of lentil (Lens culinaris) sprouts against X-ray radiation-induced cellular damage. Lentil seeds were dark germinated at low temperature and the sprout extract was prepared in PBS. Free radical scavenging of extract was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and then the radioprotective potency of extract (0 to 1000 μg/mL) on the lymphocyte cells was determined by lactate dehydrogenases assay. Moreover, micronuclei assay was assessed using the cytokinesis-block technique. The irradiations were performed using 6 MV X-ray beam. The value of IC50 for DPPH assay was 250 μg/mL. The median lethal dose for radiation was determinate at 5.37 Gy. Pretreatment with lentil sprout extract at 1000 μg/mL reduced cytotoxicity at 6 Gy total concentration from 70% to 50%. The results of micronuclei assay indicated that cells were resistant to radiation at concentrations of 500–1000 μg/mL of exogenous lentil sprout extract. The value of median effective concentration for micronuclei assay was 500 μg/mL. The results indicated that lentil sprout extract showed actually somewhat radioprotective effect on lymphocyte cell. In addition, the obtained results suggest that extract of total lentil sprout have more antioxidant activity than radicle part.

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

Cited by 7 publications

References 24 publications

Comparative study of the effects of different radiation qualities on normal human breast cells

Comparative study of the effects of different radiation qualities on normal human breast cells

Short- and long-term effects of radiation exposure at low dose and low dose rate in normal human VH10 fibroblasts

Radioprotective effects of lentil sprouts against X-ray radiation

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