Construction and validation of joint dose-response curves for chromosome aberrations and interphase lymphocyte survival for cytogenetic biodosimetry of partial exposure

Cytogenetic biodosimetry of the Partial Body Irradiation (PBI) requires a dose response curve (DRC) for chromosome aberrations (ChA) but also an exponential coefficient <i>D<sub>0</sub></i> of the interphase cell survival (<i>ICS</i>) of irradiated lymphocytes. The aim of the present work was to construct joint DRCs in vitro for ChA and <i>ICS</i> and validate them in a setting with a limited number of blood donors. Blood samples from three healthy volunteers were irradiated in vitro with 6 MV Linac photons to a range of acute doses up to 5.46 Gy. Cytogenetic preparations were stained with Fluorescence-plus-Giemsa; ChA were scored in the first division metaphases. The <i>ICS</i> was assessed in PBI simulations, mixing irradiated and unirradiated blood 1:1 at each dose point; <i>D<sub>0</sub></i> was estimated by regression analysis. The DRC for dicentrics had linear and quadratic coefficients, respectively, 0.031 × cell<sup>−1</sup> × Gy<sup>−1</sup> and 0.070 × cell<sup>−1</sup> × Gy<sup>−2</sup>; for dicentrics plus centric rings – respectively, 0.033 × cell<sup>−1</sup> × Gy<sup>−1</sup> and 0.083 × cell<sup>−1</sup> × Gy<sup>−2</sup>. The <i>ICS</i> parameter D<sub>0</sub> varied within 3.18 − 3.54 Gy, depending on the end-point used for the assessment. DRCs were successfully validated in a biodosimetry exercise with uniform irradiation and PBI simulations in vitro and using in vivo data from four breast cancer patients after their first radiotherapy dose fraction. Generating joint DRCs for ChA and <i>ICS </i>in a single experiment can be recommended as a rational methodology for laboratories practicing cytogenetic biodosimetry.

Publication Details

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Figshare
Published
2025-01-01
DOI
https://doi.org/10.6084/m9.figshare.29593341
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Legal and Regulatory Analysis
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article

Construction and validation of joint dose-response curves for chromosome aberrations and interphase lymphocyte survival for cytogenetic biodosimetry of partial exposure

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Legal and Regulatory Analysis
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Construction and validation of joint dose-response curves for chromosome aberrations and interphase lymphocyte survival for cytogenetic biodosimetry of partial exposure

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Abstract

Cytogenetic biodosimetry of the Partial Body Irradiation (PBI) requires a dose response curve (DRC) for chromosome aberrations (ChA) but also an exponential coefficient <i>D<sub>0</sub></i> of the interphase cell survival (<i>ICS</i>) of irradiated lymphocytes. The aim of the present work was to construct joint DRCs in vitro for ChA and <i>ICS</i> and validate them in a setting with a limited number of blood donors. Blood samples from three healthy volunteers were irradiated in vitro with 6 MV Linac photons to a range of acute doses up to 5.46 Gy. Cytogenetic preparations were stained with Fluorescence-plus-Giemsa; ChA were scored in the first division metaphases. The <i>ICS</i> was assessed in PBI simulations, mixing irradiated and unirradiated blood 1:1 at each dose point; <i>D<sub>0</sub></i> was estimated by regression analysis. The DRC for dicentrics had linear and quadratic coefficients, respectively, 0.031 × cell<sup>−1</sup> × Gy<sup>−1</sup> and 0.070 × cell<sup>−1</sup> × Gy<sup>−2</sup>; for dicentrics plus centric rings – respectively, 0.033 × cell<sup>−1</sup> × Gy<sup>−1</sup> and 0.083 × cell<sup>−1</sup> × Gy<sup>−2</sup>. The <i>ICS</i> parameter D<sub>0</sub> varied within 3.18 − 3.54 Gy, depending on the end-point used for the assessment. DRCs were successfully validated in a biodosimetry exercise with uniform irradiation and PBI simulations in vitro and using in vivo data from four breast cancer patients after their first radiotherapy dose fraction. Generating joint DRCs for ChA and <i>ICS </i>in a single experiment can be recommended as a rational methodology for laboratories practicing cytogenetic biodosimetry.

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