Cited by 17Radiation Therapy and DosimetryEffects of Radiation ExposureSpaceflight effects on biology

Radiobiological damage by space radiation: extension of the BIANCA model to heavy ions up to iron, and pilot application to cosmic ray exposure

Open access
Ramos, Ricardo L, Embriaco, Alessia, Carante, Mario P, Ferrari, Alfredo, Sala, Paola, Vercesi, Valerio, Ballarini, Francesca·2022·Journal of Radiological Protection

Abstract

Abstract Space research seems to be object of a renewed interest, also considering that human missions to the Moon, and possibly Mars, are being planned. Among the risks affecting such missions, astronauts’ exposure to space radiation is a major concern. In this work, the question of the evaluation of biological damage by Galactic Cosmic Rays (GCR) was addressed by a biophysical model called BIophysical ANalysis of Cell death and chromosome Aberrations (BIANCA), which simulates the induction of cell death and chromosome aberrations by different ions. While previously BIANCA has been validated for calculating cell death along hadrontherapy beams up to oxygen, herein the approach was extended up to Fe ions. Specifically, experimental survival curves available in literature for V79 cells irradiated by Si-, Ne-, Ar- and Fe-ions were reproduced, and a reference radiobiological database describing V79 cell survival as a function of ion type (1 ⩽ Z ⩽ 26), energy and dose was constructed. Analogous databases were generated for Chinese hamster ovary hamster cells and human skin fibroblasts, finding good agreement between simulations and data. Concerning chromosome aberrations, which are regarded as radiation risk biomarkers, dicentric data in human lymphocytes irradiated by heavy ions up to iron were reproduced, and a radiobiological database allowing calculation of lymphocyte dicentric yields as a function of dose, ion type (1 ⩽ Z ⩽ 26) and energy was constructed. Following interface between BIANCA and the FLUKA Monte Carlo transport code, a feasibility study was performed to calculate the relative biological effectiveness (RBE) of different GCR spectrum components, for both dicentrics and cell death. Fe-ions, although representing only 10% of the total absorbed dose, were found to be responsible for about 35%–40% of the RBE-weighted dose. Interestingly, the RBE for dicentrics was higher than that for cell survival. More generally, this work shows that BIANCA can calculate RBE values for cell death and lymphocyte dicentrics not only for ion therapy, but also for space radiation.

Integrity signals

Registry

Crossref · 10.1088/1361-6498/ac6991

Cites

39 of 39 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

5 of 19 cited sources checked · 2 supported · 1 flagged · accuracy not yet measured

  • Findingcitation

    The database describing V79 cell survival for ion beams with Z up to 8 was extended to heavier ions.

    “In this work, the database describing cell survival for ion beams with Z up to 8 was extended to heavier ions, after reproducing experimental survival curves taken from the literature for Ne-ions (LET values: 28, 42, 62, 80, 91, 110, 158, 294, 360, 448 and 452 keV µm -1 ) [23,24], Si-ions (LET: 55 keV µm -1 ) [25], Ar-ions (LET: 85 keV µm -1 ) [26] and Fe-ions (LET: 200, 440, 797 and 860 keV µm -1”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [23] Stoll, 1995, Killing and mutation of chinese hamster v79 cells exposed to accelerated oxygen and neon ions, Radiat. Res. source
    • cites [24] Antonovic, 2013, Radiobiological description of the let dependence of the cell survival of oxic and anoxic cells irradiated by carbon ions, J. Radiat. Res. source

      The Results report V79 cell-survival curves for carbon ions and test the model against neon-ion data, which supports its application to an ion heavier than Z=8. They do not describe a database covering ions up to Z=8 or its extension to the other heavier ions named in the citing sentence. Our copy provides no page numbers for these passages. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [25] Furusawa, 2017, Equivalency of the quality of sublethal lesions after photons and high-linear energy transfer ion beams, J. Radiat. Res. source
    • The authors state this as an assumption: Ionising radiation can induce DNA critical lesions (CLs), defined as lesions that interrupt chromatin fibre continuity producing two independent fragments.
    • The authors state this as an assumption: Distance-dependent incorrect rejoining of such fragments, or fragment un-rejoining, produces chromosomal aberrations.
    • The authors state this as an assumption: Certain aberration categories (dicentrics, rings and large deletions) lead to cell death.
    • The authors state this as an assumption: The dependence of chromosome-fragment rejoining probability P on fragment initial distance r is represented by a step function with value 1 below a threshold distance and 0 elsewhere, with the threshold equal to the mean distance between adjacent chromosome territories.
    • The authors state this as an assumption: Each initial fragment has a probability f to remain unrejoined, and f is an adjustable parameter.
  • Findingown data

    At 6 Gy, the simulated value overestimates the 80 keV per micrometer data by a factor of two.

    “At 6 Gy, the simulated value overestimates the 80 keV µm -1 data by a factor of two.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: Ionising radiation can induce DNA critical lesions (CLs), defined as lesions that interrupt chromatin fibre continuity producing two independent fragments.
    • The authors state this as an assumption: Distance-dependent incorrect rejoining of such fragments, or fragment un-rejoining, produces chromosomal aberrations.
    • The authors state this as an assumption: Certain aberration categories (dicentrics, rings and large deletions) lead to cell death.
    • The authors state this as an assumption: The dependence of chromosome-fragment rejoining probability P on fragment initial distance r is represented by a step function with value 1 below a threshold distance and 0 elsewhere, with the threshold equal to the mean distance between adjacent chromosome territories.
    • The authors state this as an assumption: Each initial fragment has a probability f to remain unrejoined, and f is an adjustable parameter.
  • Findingown data

    For chromosome aberrations, data on specific aberration categories in human lymphocytes were better reproduced by describing the dependence of P on r by an exponential function.

    “Concerning chromosome aberrations, we have found that the data on specific aberration categories in human lymphocytes were better reproduced by describing the dependence of P on r by means of an exponential function of the form:”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [12] Tello Cajiao, 2017, Proximity effects in chromosome aberration induction by low-LET ionizing radiation, DNA Repair source
    • cites [13] Tello Cajiao, 2018, Proximity effects in chromosome aberration induction: dependence on radiation quality, cell type and dose, DNA Repair source
    • The authors state this as an assumption: For chromosome aberrations, the dependence of P on r is described by an exponential function P(r)=e^{-r/r0}, with r0 fixed to 0.8 micrometers.
  • Findingown data

    At 5 Gy, simulation outcomes overestimate the data by a factor up to 3.5.

    “At 5 Gy, the simulation outcomes overestimate the data by a factor up to 3.5.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: Ionising radiation can induce DNA critical lesions (CLs), defined as lesions that interrupt chromatin fibre continuity producing two independent fragments.
    • The authors state this as an assumption: Distance-dependent incorrect rejoining of such fragments, or fragment un-rejoining, produces chromosomal aberrations.
    • The authors state this as an assumption: Certain aberration categories (dicentrics, rings and large deletions) lead to cell death.
    • The authors state this as an assumption: The dependence of chromosome-fragment rejoining probability P on fragment initial distance r is represented by a step function with value 1 below a threshold distance and 0 elsewhere, with the threshold equal to the mean distance between adjacent chromosome territories.
    • The authors state this as an assumption: Each initial fragment has a probability f to remain unrejoined, and f is an adjustable parameter.
  • Findingown data

    For each ion type and LET, the CL yield and un-rejoining fraction were adjusted following comparison with the data.

    “For each ion type and LET, the values of the CL yield and the un-rejoining fraction were adjusted following comparison with the data.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: Ionising radiation can induce DNA critical lesions (CLs), defined as lesions that interrupt chromatin fibre continuity producing two independent fragments.
    • The authors state this as an assumption: Distance-dependent incorrect rejoining of such fragments, or fragment un-rejoining, produces chromosomal aberrations.
    • The authors state this as an assumption: Certain aberration categories (dicentrics, rings and large deletions) lead to cell death.
    • The authors state this as an assumption: The dependence of chromosome-fragment rejoining probability P on fragment initial distance r is represented by a step function with value 1 below a threshold distance and 0 elsewhere, with the threshold equal to the mean distance between adjacent chromosome territories.
    • The authors state this as an assumption: Each initial fragment has a probability f to remain unrejoined, and f is an adjustable parameter.
  • May combine two claims. 15
  • Classified as probably not a substantial claim. 3
  • The quote only partly states this claim. 3
  • May combine two claims.

    Premisecitation

    The relative contribution to the GCR total dose is about 40% for protons, 20% for He-ions, 10% for Fe-ions, and 30% for ions between Helium and Iron.

    “considering that the relative contribution to the GCR total dose is about 40% for protons, 20% for He-ions, 10% for Fe-ions, and 30% for ions between Helium and Iron [38]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [38] Simonsen, 2020, NASA’s first ground-based galactic cosmic ray simulator: enabling a new era in space radiobiology research, PLoS Biol. source

      In Methods and models, ‘Determination of GCR reference environment’ (page unavailable), the paper assigns approximately 64% of dose to Z = 1 ions, 17% to helium ions, and 7% to all heavier ions combined in its shielded reference field. Those figures contradict the claimed 40% for protons and 40% collectively for iron and other heavier ions. The paper also distinguishes absorbed dose from dose equivalent, for which it gives a different figure for iron. (LLM, conf=0.90)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Lymphocyte dicentrics are considered among the best biomarkers of normal tissue damage risk.

    “More recently, we have developed an analogous database to simulate dicentric dose-response in human lymphocytes, which are considered among the best biomarkers of normal tissue damage risk [See, e.g. 2, 8, 18 -20].”
    Quote in the paperNot a substantial claim1 of 5 sources checked
    • cites [2] Cucinotta, 2008, Physical and biological organ dosimetry analysis for international space station astronauts, Radiat. Res. source
    • cites [8] Durante, 2002, Radiation protection in space, Riv. Nuovo Cimento source
    • cites [18] Bonassi, 2000, Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens, Cancer Res.

      Not checked in the free run.

    • cites [19] Bonassi, 2008, Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries, Carcinogenesis source

      The Introduction and Discussion describe chromosomal aberrations in lymphocytes as biomarkers of cancer risk. The Results include dicentrics among the aberrations studied, but report a non-significant association for them; the paper does not identify dicentrics as among the best biomarkers of normal tissue damage risk. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [20] Ballarini, 2003, Chromosome aberrations as biomarkers of radiation exposure: modelling basic mechanisms, Adv. Space Res. source
  • May combine two claims.

    Findingown data

    For CHO cells, the maximum percentage displacement between simulations and data is 10% at 200 keV per micrometer from [28], 10% at 780 keV per micrometer, 25% at 1200 keV per micrometer, and 25% at 2000 keV per micrometer.

    “In particular, the maximum percentage displacement between simulations and data is 10% for the 200 keV µm -1 data taken from [28], 10% at 780 keV µm -1 , 25% at 1200 keV µm -1 , and 25% at 2000 keV µm -1 .”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [28] Sunada, 2017, Investigation of the relative biological effectiveness and uniform isobiological killing effects of irradiation with a clinical carbon SOBP beam on DNA repair deficient CHO cells, Oncol. Lett. source
    • The authors state this as an assumption: Ionising radiation can induce DNA critical lesions (CLs), defined as lesions that interrupt chromatin fibre continuity producing two independent fragments.
    • The authors state this as an assumption: Distance-dependent incorrect rejoining of such fragments, or fragment un-rejoining, produces chromosomal aberrations.
    • The authors state this as an assumption: Certain aberration categories (dicentrics, rings and large deletions) lead to cell death.
    • The authors state this as an assumption: The dependence of chromosome-fragment rejoining probability P on fragment initial distance r is represented by a step function with value 1 below a threshold distance and 0 elsewhere, with the threshold equal to the mean distance between adjacent chromosome territories.
    • The authors state this as an assumption: Each initial fragment has a probability f to remain unrejoined, and f is an adjustable parameter.
  • May combine two claims.

    Findingown data

    The simulated curves were obtained using CL yields in the range 0.011-0.302 CL per micrometer, increasing with LET.

    “The simulated curves were obtained using CL yields in the range 0.011-0.302CL µm -1 , increasing with LET.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: Ionising radiation can induce DNA critical lesions (CLs), defined as lesions that interrupt chromatin fibre continuity producing two independent fragments.
    • The authors state this as an assumption: Distance-dependent incorrect rejoining of such fragments, or fragment un-rejoining, produces chromosomal aberrations.
    • The authors state this as an assumption: Certain aberration categories (dicentrics, rings and large deletions) lead to cell death.
    • The authors state this as an assumption: The dependence of chromosome-fragment rejoining probability P on fragment initial distance r is represented by a step function with value 1 below a threshold distance and 0 elsewhere, with the threshold equal to the mean distance between adjacent chromosome territories.
    • The authors state this as an assumption: Each initial fragment has a probability f to remain unrejoined, and f is an adjustable parameter.
  • May combine two claims.

    Findingown data

    In figure 1(b), simulations well reproduce the data up to 4 Gy, with differences lower than 30%.

    “In figure 1(b) the simulations well reproduce the data up to 4 Gy.In these cases, the differences between simulations and data remain lower than 30%.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: Ionising radiation can induce DNA critical lesions (CLs), defined as lesions that interrupt chromatin fibre continuity producing two independent fragments.
    • The authors state this as an assumption: Distance-dependent incorrect rejoining of such fragments, or fragment un-rejoining, produces chromosomal aberrations.
    • The authors state this as an assumption: Certain aberration categories (dicentrics, rings and large deletions) lead to cell death.
    • The authors state this as an assumption: The dependence of chromosome-fragment rejoining probability P on fragment initial distance r is represented by a step function with value 1 below a threshold distance and 0 elsewhere, with the threshold equal to the mean distance between adjacent chromosome territories.
    • The authors state this as an assumption: Each initial fragment has a probability f to remain unrejoined, and f is an adjustable parameter.
  • May combine two claims.

    Findingown data

    Figure 1(a) shows good agreement between simulations and data up to 5 Gy, with differences below 20%.

    “Figure 1(a) shows a good agreement between simulations and data up to 5 Gy, where the differences between data and calculations remained below 20%.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: Ionising radiation can induce DNA critical lesions (CLs), defined as lesions that interrupt chromatin fibre continuity producing two independent fragments.
    • The authors state this as an assumption: Distance-dependent incorrect rejoining of such fragments, or fragment un-rejoining, produces chromosomal aberrations.
    • The authors state this as an assumption: Certain aberration categories (dicentrics, rings and large deletions) lead to cell death.
    • The authors state this as an assumption: The dependence of chromosome-fragment rejoining probability P on fragment initial distance r is represented by a step function with value 1 below a threshold distance and 0 elsewhere, with the threshold equal to the mean distance between adjacent chromosome territories.
    • The authors state this as an assumption: Each initial fragment has a probability f to remain unrejoined, and f is an adjustable parameter.
  • May combine two claims.

    Findingreasoning

    Two radiobiological databases for ions with 1 <= Z <= 26 were constructed, one describing cell death for human fibroblasts and another describing dicentric induction in human lymphocytes.

    “More specifically, two radiobiological databases for these ions (1 ⩽ Z ⩽ 26) were constructed, one describing cell death for human fibroblasts, and another one describing dicentric induction in human lymphocytes.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: Ionising radiation can induce DNA critical lesions (CLs), defined as lesions that interrupt chromatin fibre continuity producing two independent fragments.
    • The authors state this as an assumption: Distance-dependent incorrect rejoining of such fragments, or fragment un-rejoining, produces chromosomal aberrations.
    • The authors state this as an assumption: Certain aberration categories (dicentrics, rings and large deletions) lead to cell death.
    • The authors state this as an assumption: The dependence of chromosome-fragment rejoining probability P on fragment initial distance r is represented by a step function with value 1 below a threshold distance and 0 elsewhere, with the threshold equal to the mean distance between adjacent chromosome territories.
    • The authors state this as an assumption: Each initial fragment has a probability f to remain unrejoined, and f is an adjustable parameter.
    • The authors state this as an assumption: For chromosome aberrations, the dependence of P on r is described by an exponential function P(r)=e^{-r/r0}, with r0 fixed to 0.8 micrometers.
  • May combine two claims. The quote only partly states this claim.

    Findingown data

    For AG01522 cells exposed to C-ion beams, the maximum difference between data and simulations is 35% at 48 keV per micrometer; at 76.3 keV per micrometer simulations are within the experimental error bar except at 4 Gy; at 108 keV per micrometer the difference reaches 40% at 2 Gy and simulations underestimate the data by a factor of 2.5 at 3 Gy; at 147.6 keV per micrometer the maximum difference,

    “Specifically, at 48 keV µm -1 the maximum difference between data and simulations is 35%; at 76.3 keV µm -1 the simulation results are within the experimental error bar for each considered experimental point, with the only exception of the point at 4 Gy; at 108 keV µm -1 , the difference between predictions and data reaches 40% at 2 Gy, whereas at 3 Gy the simulation outcomes underestimate the”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: Ionising radiation can induce DNA critical lesions (CLs), defined as lesions that interrupt chromatin fibre continuity producing two independent fragments.
    • The authors state this as an assumption: Distance-dependent incorrect rejoining of such fragments, or fragment un-rejoining, produces chromosomal aberrations.
    • The authors state this as an assumption: Certain aberration categories (dicentrics, rings and large deletions) lead to cell death.
    • The authors state this as an assumption: The dependence of chromosome-fragment rejoining probability P on fragment initial distance r is represented by a step function with value 1 below a threshold distance and 0 elsewhere, with the threshold equal to the mean distance between adjacent chromosome territories.
    • The authors state this as an assumption: Each initial fragment has a probability f to remain unrejoined, and f is an adjustable parameter.
  • May combine two claims.

    Findingreasoning

    At 440 keV per micrometer, the mean number of traversals per cell after 1 Gy is 0.4, implying that about 67% of cells are not traversed by any particle.

    “For instance, at 440 keV µm -1 the mean number of traversals per cell after 1 Gy is 0.4, which implies that about 67% of the cells are not traversed by any particle.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingcitation

    Fe-ions, although representing only 10% of the total absorbed dose, were responsible for more than 40% of the RBE-weighted dose when RBE_dic was considered, and about 35% when RBE_surv was considered.

    “The results for the RBE-weighted dose show that Fe-ions, although representing only 10% of the total absorbed dose, were responsible for more than 40% of the RBE-weighted dose when RBE dic was considered, and about 35% when RBE surv was considered, confirming the high effectiveness of these ions [See, e.g.39].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [39] Campa, 2009, DNA fragmentation induced in human fibroblasts by 56Fe ions: experimental data and MC simulations, Radiat. Res. source
    • The authors state this as an assumption: C-ions are representative of the ions between Helium and Iron.
  • May combine two claims.

    Findingown data

    BIANCA was interfaced with FLUKA and the RBE of the main GCR spectrum components was calculated, both for dicentrics and cell death.

    “As a feasibility study, BIANCA was interfaced with the FLUKA transport code and the RBE of the main CGR spectrum components was calculated, both for dicentrics and for cell death.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: C-ions are representative of the ions between Helium and Iron.
  • May combine two claims.

    Findingown data

    For the 200 keV per micrometer CHO data from [29], the difference is 25% up to 4 Gy, while at 6 Gy the simulation approximately duplicates the experimental value.

    “Concerning the 200 keV µm -1 data taken from [29], this difference is 25% for dose values up to 4 Gy, whereas at 6 Gy the simulation results approximately duplicate the experimental value.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Okayasu, 2006, Repair of DNA damage induced by accelerated heavy ions in mammalian cells proficient and deficient in the non-homologous end-joining pathway, Radiat. Res. source
    • The authors state this as an assumption: Ionising radiation can induce DNA critical lesions (CLs), defined as lesions that interrupt chromatin fibre continuity producing two independent fragments.
    • The authors state this as an assumption: Distance-dependent incorrect rejoining of such fragments, or fragment un-rejoining, produces chromosomal aberrations.
    • The authors state this as an assumption: Certain aberration categories (dicentrics, rings and large deletions) lead to cell death.
    • The authors state this as an assumption: The dependence of chromosome-fragment rejoining probability P on fragment initial distance r is represented by a step function with value 1 below a threshold distance and 0 elsewhere, with the threshold equal to the mean distance between adjacent chromosome territories.
    • The authors state this as an assumption: Each initial fragment has a probability f to remain unrejoined, and f is an adjustable parameter.
  • May combine two claims.

    Findingown data

    Figure 6(b) shows general good agreement between simulations and data for He-ion beams, since for doses up to 4 Gy the simulation results are within the experimental error bar with two exceptions, the highest doses at 16.2 keV per micrometer.

    “Figure 6(b) shows a general good agreement between simulations and data, since for doses up to 4 Gy the simulation results are within the experimental error bar with two exceptions, that is the highest doses at 16.2 keV µm -1 .”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: Ionising radiation can induce DNA critical lesions (CLs), defined as lesions that interrupt chromatin fibre continuity producing two independent fragments.
    • The authors state this as an assumption: Distance-dependent incorrect rejoining of such fragments, or fragment un-rejoining, produces chromosomal aberrations.
    • The authors state this as an assumption: Certain aberration categories (dicentrics, rings and large deletions) lead to cell death.
    • The authors state this as an assumption: The dependence of chromosome-fragment rejoining probability P on fragment initial distance r is represented by a step function with value 1 below a threshold distance and 0 elsewhere, with the threshold equal to the mean distance between adjacent chromosome territories.
    • The authors state this as an assumption: Each initial fragment has a probability f to remain unrejoined, and f is an adjustable parameter.
  • May combine two claims.

    Findingreasoning

    At 155 keV per micrometer, the mean number of traversals per cell at 1 Gy is 1.14, about 32% of cells are not traversed, and the other 68% are hit by at least one particle.

    “On the contrary at 155 keV µm -1 the mean number of traversals per cell at 1 Gy is 1.14, and thus about 32% are not traversed, whereas the other 68% are hit by at least one particle.”
    Quote in the paperNot a substantial claim
  • The quote only partly states this claim.

    Findingown data

    For Ar and Fe beams, a f value equal to 0.20 allowed obtaining good agreement with the data.

    “Like for Ne and Si, a f value equal to 0.20 allowed obtaining a good agreement with the data.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: Each initial fragment has a probability f to remain unrejoined, and f is an adjustable parameter.
  • May combine two claims.

    Findingown data

    For HSF cells, the maximum percentage displacement between simulations and data fit is 30% at 200 keV per micrometer, 10% at 300 keV per micrometer, and 20% at 500 keV per micrometer.

    “The maximum percentage displacement between simulations and data fit is 30% at 200 keV µm -1 , 10% at 300 keV µm -1 and 20% at 500 keV µm -1 .”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: Ionising radiation can induce DNA critical lesions (CLs), defined as lesions that interrupt chromatin fibre continuity producing two independent fragments.
    • The authors state this as an assumption: Distance-dependent incorrect rejoining of such fragments, or fragment un-rejoining, produces chromosomal aberrations.
    • The authors state this as an assumption: Certain aberration categories (dicentrics, rings and large deletions) lead to cell death.
    • The authors state this as an assumption: The dependence of chromosome-fragment rejoining probability P on fragment initial distance r is represented by a step function with value 1 below a threshold distance and 0 elsewhere, with the threshold equal to the mean distance between adjacent chromosome territories.
    • The authors state this as an assumption: Each initial fragment has a probability f to remain unrejoined, and f is an adjustable parameter.
  • May combine two claims.

    Findingreasoning

    The 440 keV per micrometer beam is less effective than the 335 keV per micrometer one, which in turn is less effective than the 155 keV per micrometer beam.

    “As expected, the 440 keV µm -1 beam is less effective than the 335 keV µm -1 one, which in turn is less effective than the 155 keV µm -1 beam.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: Ionising radiation can induce DNA critical lesions (CLs), defined as lesions that interrupt chromatin fibre continuity producing two independent fragments.
    • The authors state this as an assumption: Distance-dependent incorrect rejoining of such fragments, or fragment un-rejoining, produces chromosomal aberrations.
    • The authors state this as an assumption: Certain aberration categories (dicentrics, rings and large deletions) lead to cell death.
    • The authors state this as an assumption: The dependence of chromosome-fragment rejoining probability P on fragment initial distance r is represented by a step function with value 1 below a threshold distance and 0 elsewhere, with the threshold equal to the mean distance between adjacent chromosome territories.
    • The authors state this as an assumption: Each initial fragment has a probability f to remain unrejoined, and f is an adjustable parameter.
    • The authors state this as an assumption: For chromosome aberrations, the dependence of P on r is described by an exponential function P(r)=e^{-r/r0}, with r0 fixed to 0.8 micrometers.
  • The quote only partly states this claim.

    Findingown data

    Figure 6(a) shows a general tendency to underestimate the AG01522 data for C-ion beams.

    “Figure 6(a) shows a general tendency to underestimate the data.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: Ionising radiation can induce DNA critical lesions (CLs), defined as lesions that interrupt chromatin fibre continuity producing two independent fragments.
    • The authors state this as an assumption: Distance-dependent incorrect rejoining of such fragments, or fragment un-rejoining, produces chromosomal aberrations.
    • The authors state this as an assumption: Certain aberration categories (dicentrics, rings and large deletions) lead to cell death.
    • The authors state this as an assumption: The dependence of chromosome-fragment rejoining probability P on fragment initial distance r is represented by a step function with value 1 below a threshold distance and 0 elsewhere, with the threshold equal to the mean distance between adjacent chromosome territories.
    • The authors state this as an assumption: Each initial fragment has a probability f to remain unrejoined, and f is an adjustable parameter.
  • Classified as probably not a substantial claim.

    Premisecitation

    The features of DNA lesions leading to chromosomal aberrations and cell death are still an open question after more than two decades.

    “Since the features of the DNA lesions leading to chromosomal aberrations and cell death are still an open question after more than two decades [See, e.g.14]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14] Ottolenghi, 1999, Modelling radiation induced biological lesions: from initial energy depositions to chromosome aberrations, Radiat. Environ. Biophys. source
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    In the current version of BIANCA, the fact that dicentric yields tend to increase with sampling time is taken into account only implicitly, by adjusting the CL yield.

    “It is worth mentioning that in the current version of BIANCA, the fact that the dicentric yields tend to increase with the sampling time is taken into account only implicitly, by adjusting the CL yield.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: Ionising radiation can induce DNA critical lesions (CLs), defined as lesions that interrupt chromatin fibre continuity producing two independent fragments.
    • The authors state this as an assumption: Distance-dependent incorrect rejoining of such fragments, or fragment un-rejoining, produces chromosomal aberrations.
    • The authors state this as an assumption: Certain aberration categories (dicentrics, rings and large deletions) lead to cell death.
    • The authors state this as an assumption: The dependence of chromosome-fragment rejoining probability P on fragment initial distance r is represented by a step function with value 1 below a threshold distance and 0 elsewhere, with the threshold equal to the mean distance between adjacent chromosome territories.
    • The authors state this as an assumption: Each initial fragment has a probability f to remain unrejoined, and f is an adjustable parameter.
    • The authors state this as an assumption: For chromosome aberrations, the dependence of P on r is described by an exponential function P(r)=e^{-r/r0}, with r0 fixed to 0.8 micrometers.
20 of 20
  • The authors state this as an assumption.

    Ionising radiation can induce DNA critical lesions (CLs), defined as lesions that interrupt chromatin fibre continuity producing two independent fragments.

    “(a) ionising radiation can induce DNA 'critical lesions' (CLs), where a CL is defined as a lesion that interrupts the chromatin fibre continuity producing two (main) independent fragments;”
  • The authors state this as an assumption.

    Distance-dependent incorrect rejoining of such fragments, or fragment un-rejoining, produces chromosomal aberrations.

    “(b) distance-dependent incorrect rejoining of such fragments, or fragment un-rejoining, produces chromosomal aberrations;”
  • The authors state this as an assumption.

    Certain aberration categories (dicentrics, rings and large deletions) lead to cell death.

    “(c) certain aberration categories (dicentrics, rings and large deletions, where 'large' means visible when chromatin is condensed) lead to cell death.”
  • The authors state this as an assumption.

    The dependence of chromosome-fragment rejoining probability P on fragment initial distance r is represented by a step function with value 1 below a threshold distance and 0 elsewhere, with the threshold equal to the mean distance between adjacent chromosome territories.

    “Previous works on cell survival have shown that the experimental data can be reproduced by assuming that the dependence of the chromosome-fragment rejoining probability, P, on the fragment initial distance, r, is represented by a step function whose value is 1 below a certain threshold distance, and 0 elsewhere; the threshold value have been set equal to the mean distance between two adjacent”
  • The authors state this as an assumption.

    Each initial fragment has a probability f to remain unrejoined, and f is an adjustable parameter.

    “In these simulations, each initial fragment has a certain probability, f, to remain unrejoined, and f is the second, and last, adjustable parameter.”
  • The authors state this as an assumption.

    For chromosome aberrations, the dependence of P on r is described by an exponential function P(r)=e^{-r/r0}, with r0 fixed to 0.8 micrometers.

    “Concerning chromosome aberrations, we have found that the data on specific aberration categories in human lymphocytes were better reproduced by describing the dependence of P on r by means of an exponential function of the form:”
    “where r 0 has been fixed to 0.8 µm [12,13].”
  • The authors state this as an assumption.

    C-ions are representative of the ions between Helium and Iron.

    “C-ions were considered as representative of the ions between Helium and Iron.”
7 of 7

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • The ion-coefficient rules omit atomic number 15

    Minor

    The paper says its databases cover ions with atomic numbers 1 through 26, but its stated rules for assigning cell-survival coefficients cover 9-14 and then numbers greater than 15. They leave Z = 15 unassigned.

  • The cited prior dicentric study does not match reference 22

    Minor

    The text identifies reference 22 as a prior study that constructed a BIANCA dicentric database. The reference list instead identifies it as a 1980 paper on the synergistic effects of different radiations.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Bonassi, 2000, Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens, Cancer Res., 60, 1619

Cited by

Sorted by citations

Authors
Ramos, R. L., Embriaco, A., Carante, M. P., Ferrari, A., Sala, P., Vercesi, V., & Ballarini, F.
Affiliations
  • Istituto Nazionale di Fisica Nucleare, Sezione di Pavia (IT)
  • National Agency for New Technologies, Energy and Sustainable Economic Development (IT)
  • University of Pavia (IT)
  • Gangneung–Wonju National University (KR)
  • Istituto Nazionale di Fisica Nucleare, Sezione di Milano (IT)
Corresponding author
  • Ramos, Ricardo L
  • Embriaco, Alessia
  • Carante, Mario P
  • Ferrari, Alfredo
  • Sala, Paola
  • Vercesi, Valerio
  • Ballarini, Francesca
Venue
Journal of Radiological Protection
Published
2022-05-04
Volume
42
Issue
2
Pages
021523
ISSN
  • 0952-4746 (ISSN-L)
  • 1361-6498
OpenAlex
W4224253096
Cited by
17
References
39
Citations by year
2026: 6 · 2025: 3 · 2024: 6 · 2023: 2
FWCI
1.77
Type
journal article
Language
en
Open access
Locations
  • Journal of Radiological Protection (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • MIUR Dipartimenti di Eccellenza (1161908)
  • Research Ministry
  • INFN (MC-INFN/FLUKA)
  • Regione Lombardia (INSpIRIT)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
  • Health Sciences › Medicine › Physiology › Spaceflight effects on biology
Keywords
space radiation, galactic cosmic rays, heavy ions, iron ions, cell survival, chromosomal abnormalities, relative biological effectiveness, V79 cells, CHO cells, human dermal fibroblasts, lymphocytes, FLUKA, astronaut radiation risk, cosmic ray exposure
MeSH terms
Animals, Chromosome Aberrations, Cosmic Radiation, Cricetulus, Cricetinae, Humans, Iron, CHO Cells, Cell Death, Heavy Ions

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-11.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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