Investigation of DNA Damage and Cell-Cycle Distribution in Human Peripheral Blood Lymphocytes under Exposure to High Doses of Proton Radiotherapy

Miszczyk, Justyna

doi:10.3390/biology10020111

Cited by 3 publications

(5 citation statements)

References 46 publications

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“…The extent of the observed delay was dependent on the delivered dose, as demonstrated by chasing the cells through prolonged culture times. This observation is in agreement with previous reports 50 , 51 . Markedly, our results show similar kinetics for G1 phase-entry between non-irradiated cells and cells exposed to 2 Gy of X-rays, although there is a ~ 2 h-delay.…”

Section: Discussionsupporting

confidence: 94%

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An updated view into the cell cycle kinetics of human T lymphocytes and the impact of irradiation

Vral

Baeyens

2022

Sci Rep

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Even though a detailed understanding of the proliferative characteristics of T lymphocytes is imperative in many research fields, prior studies have never reached a consensus on these characteristics, and on the corresponding cell cycle kinetics specifically. In this study, the general proliferative response of human T lymphocytes to phytohaemagglutinin (PHA) stimulation was characterized using a carboxyfluorescein succinimidyl ester-based flow cytometric assay. We were able to determine when PHA-stimulated T lymphocytes complete their first division, the proportion of cells that initiate proliferation, the subsequent division rate of the cells, and the impact of irradiation on these proliferative properties. Next, we accurately visualized the cell cycle progression of dividing T lymphocytes cultured in whole blood using an adapted 5-ethynyl-2’-deoxyuridine pulse-chase method. Furthermore, through multiple downstream analysis methods, we were able to make an estimation of the corresponding cell cycle kinetics. We also visualized the impact of X-rays on the progression of the cells through the cell cycle. Our results showed dose-dependent G2 arrest after exposure to irradiation, and a corresponding delay in G1 phase-entry of the cells. In conclusion, utilizing various flow cytometric assays, we provided valuable information on T lymphocyte proliferation characteristics starting from first division to fully dividing cells.

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Section: Discussionsupporting

confidence: 94%

“…In recent years, considerable progress has been made towards understanding the precise mechanisms involved in cell cycle progression, checkpoints, and DNA repair 50 , 53 , 55 . However, the cell cycle is regulated by a complex network and is influenced not only by intracellular signals, but also by extracellular factors.…”

Section: Discussionmentioning

confidence: 99%

An updated view into the cell cycle kinetics of human T lymphocytes and the impact of irradiation

Vral

Baeyens

2022

Sci Rep

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“…The radio-sensitivity of lymphocytes irradiated in vitro with protons may not be differ (though more pronounced) from x-ray effects 24,25 . It could be mediated by changes in cells and tissues that could, in turn, modulate the RIL extent.…”

Section: Introductionmentioning

confidence: 89%

“…Taken together, these data suggest that proton therapy would likely be of interest to protect lymphocytes and preserve the anti-tumoral immune response. The radio-sensitivity of lymphocytes irradiated in vitro with protons may not be differ (though more pronounced) from x-ray effects 24,25 . It could be mediated by changes in cells and tissues that could, in turn, modulate the RIL extent.…”

Section: Introductionmentioning

confidence: 89%

Investigating the effects of protons versus x-rays on radiation-induced lymphopenia after brain irradiation

Coupey,

Pham,

Toutain

et al. 2024

Preprint

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Background: Conventional x-ray-based radiotherapy is a standard treatment for patients with brain tumors. However, is associated with systemic effects like lymphopenia that correlates with poor prognosis. Proton therapy has emerged as a new radiation strategy, given that the lower entry dose and absence of exit dose can be exploited to spare healthy brain tissues and reduce side-effects caused by systemic inflammation. We evaluated if brain irradiation with protons could spare circulating leukocytes along with other variables in rodent models. Methods: Tumor-free C57BL/6 mice were irradiated with a total dose of 20Gy in 2.5Gy twice-daily sessions over four consecutive days with either x-rays or protons. Groups of mice were defined according to irradiation volume (whole-brain or hemisphere) and dose rate (1 or 2Gy/min). Blood was withdrawn at various time points and circulating lymphoid, with myeloid subpopulations analyzed using flow cytometry. Brain tissue histochemical analyses were performed late after irradiation. Results: Blood sampling showed severe and acute radiation-induced lymphopenia after x-rays, with marked depletion of 50% CD4+ and CD8+, as well as B and NK cells. With protons, the decrease was 20% on average for whole-brain irradiations, suggesting a conservative effect on circulating lymphocytes. The data showed no effect in CD11b+ myeloid cells for both x-rays and protons. Histological analyses revealed a more intense expression level of CD68 and Iba1 immunostaining after x-ray irradiation. GFAP staining was well detected after both beams. Conclusion: Proton therapy for brain tumors differs from photon therapy in terms of its effects on circulating cells and tissues.

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“…Ring frequencies were documented solely for cells in the G1, G2, metaphase, and anaphase phases. The morphology of chromosomes in PCCr cells varies depending on the phase of the cell cycle when premature condensation is induced: [13], [14] • G1: Characterized by univalent chromosomes (unduplicated DNA, single chromatid).…”

Section: Analysis Criteria For the Pccr Assay And For Scoring Chromos...mentioning

confidence: 99%

Curva de calibración dosis-efecto para altas dosis de rayos X utilizando el ensayo de condensación prematura de cromosomas con Caliculina-A

Chaves-Campos,

Ortíz-Morales,

Mejías-Gamboa

et al. 2024

Braz. J. Rad. Sci.

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Purpose: This article shows the results of the Cytogenetics Laboratory of the Health Research Institute (INISA) to develop a dose-effect calibration curve with the Calyculin-A chemical induction premature condensation assay to estimate high doses of X-ray exposure. Methods: to create the calibration curve, peripheral blood samples from two participants (one female and one male) were exposed to X-rays at six different dose points ranging from 0 to 17.5 Gy in vitro. The irradiated blood was cultured for 48 hours according to international protocols, and the resulting chromosome rings were recorded. We used BioDoseTools software to calculate the coefficients for the calibration curve. Results: The coefficients of the curve are α: 0.028±0.001 and C: 0.001±0.001. These coefficients have similar values to those reported internationally. The curve was validated by calculating an unknown dose exposed to 6 Gy; the estimated dose was 5.651 ± 0.636 Gy, with no statistically significant differences between the dose delivered and the estimated dose. Conclusions: The INISA Biological Dosimetry Service can use the curve obtained to assess absorbed doses in cases of suspected overexposure to high X-ray doses.

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Investigation of DNA Damage and Cell-Cycle Distribution in Human Peripheral Blood Lymphocytes under Exposure to High Doses of Proton Radiotherapy

Cited by 3 publications

References 46 publications

An updated view into the cell cycle kinetics of human T lymphocytes and the impact of irradiation

An updated view into the cell cycle kinetics of human T lymphocytes and the impact of irradiation

Investigating the effects of protons versus x-rays on radiation-induced lymphopenia after brain irradiation

Curva de calibración dosis-efecto para altas dosis de rayos X utilizando el ensayo de condensación prematura de cromosomas con Caliculina-A

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