Comparative study of micronucleus assays and dicentric plus ring chromosomes for dose assessment in particular cases of partial-body exposure

Mendes, Mariana Esposito; Mendonça, Julyanne C G; Barquinero, Joan Francesc; Higueras, Manuel; González, Jorge E.; Andrade, Aida M G; Silva, Laís M; Nascimento, Alyne M S; Lima, Julianne C F; Silva, Júlio C. G.; Hwang, Suy; Melo, Ana Maria Mendonça de Albuquerque; Santos, Neide; Lima, F. F.

doi:10.1080/09553002.2019.1607606

Cited by 10 publications

(16 citation statements)

References 38 publications

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“…To address these issues, there are many advanced techniques for dose reconstruction for complex exposure scenarios, which are generally based on fitting parametric linear or linear quadratic dose response functions with selected error distributions (e.g. Zero-Inflated Poisson or Negative Binomial) 31,40,42,43 . Here we extended the analysis of micronuclei per cell distribution shapes in a different direction: we used various summary metrics like index of dispersion, skewness and kurtosis as potential predictors of complex exposure scenarios, and imported these predictors into machine learning or parametric regression methods.…”

Section: Discussionmentioning

confidence: 99%

“…There is a large body of literature on various computational biodosimetry approaches for estimating radiation doses in various exposure scenarios based on micronuclei yields and other cytogenetics markers like dicentric chromosomes [22][23][24][25][26][27][28][29][30][31][32] . As compared to uniform photon exposures, both neutron and partial body exposures result in a non-poissonian distribution of damage in the cells scored for biodosimetry due to the shielding and/or differences in radiation track structure and energy deposition patterns.…”

Section: Current Approaches For Evaluating Complex Exposuresmentioning

confidence: 99%

“…frequentist vs. Bayesian techniques), a more common popular approach is to fit selected probability density functions (e.g. Zero-Inflated Poisson or Negative Binomial) to the data 31,42,43 .…”

Section: Current Approaches For Evaluating Complex Exposuresmentioning

confidence: 99%

“…This phenomenon was the rationale for using the variable LnSum. The other variables listed in Table 1 were used based on our judgement of what metrics could act as reasonable potential predictors of exposure type and/or dose, combined with information about overdispersion of cytogenetic damage from complex exposure scenarios 31,38,39 . Table 1.…”

Section: Development Of Predictor Setsmentioning

confidence: 99%

“…M is the mean, V is the variance, and n is the number of cells in the analyzed sample. The predictor variables were selected based on our judgement, combined with information about overdispersion of cytogenetic damage from complex exposure scenarios 31,38,39 .…”

Section: Author Contributionsmentioning

confidence: 99%

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New High Throughput Approaches to Detect Partial-body and Neutron Exposures on an Individual Basis

Shuryak

Turner

Perrier

et al. 2019

Preprint

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Biodosimetry-based discrimination between homogeneous total-body photon exposure and complex irradiation scenarios (partial-body shielding and/or neutron + photon mixtures) can improve treatment decisions after mass-casualty radiation-related incidents. Our study objective was to use high-throughput biomarkers to: a) detect partial-body and/or neutron exposure on an individual basis, and b) estimate separately the photon and neutron doses in a mixed exposure.We developed a novel approach, where metrics related to the shapes of micronuclei distributions per binucleated cell in ex-vivo irradiated human lymphocytes (variance/mean, kurtosis, skewness, etc.) served as predictors in machine learning or parametric analyses of the following scenarios: (A) Homogeneous gamma-irradiation, mimicking total-body exposures, vs. mixtures of irradiated blood with unirradiated blood, mimicking partial-body exposures. (B) X rays vs. various neutron + photon mixtures. Classification of samples as homogeneously vs. heterogeneously irradiated (scenario A) achieved a receiver operating characteristic curve area (AUROC) of 0.931 (uncertainty range of 0.903-0.951), and R 2 for actual vs. reconstructed mean dose was 0.87. Detection of samples with ≥ 10% neutron contribution (scenario B) achieved AUROC of 0.916 (0.893-0.943), and R 2 for reconstructing photon-equivalent dose was 0.77. These encouraging findings demonstrate a proof-of-principle for the proposed approach of analyzing micronuclei/cell distributions to detect clinically-relevant complex radiation exposure scenarios.biodosimetry approach in this scenario was to distinguish neutron + photon mixtures from pure photon exposures, and to quantify the neutron contribution.

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Section: Discussionmentioning

confidence: 99%

Section: Current Approaches For Evaluating Complex Exposuresmentioning

confidence: 99%

Section: Current Approaches For Evaluating Complex Exposuresmentioning

confidence: 99%

Section: Development Of Predictor Setsmentioning

confidence: 99%

Section: Author Contributionsmentioning

confidence: 99%

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New High Throughput Approaches to Detect Partial-body and Neutron Exposures on an Individual Basis

Shuryak

Turner

Perrier

et al. 2019

Preprint

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Derivation of Optimal Experimental Design Methods for Applications in Cytogenetic Biodosimetry

Higueras

López–Fidalgo

2023

Statistical Methods at the Forefront of Biomedical Advances

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The relationship of the efficiency of energy conversion into growth as an indicator for the determination of the optimal dose for mutation breeding with the appearance of chromosomal abnormalities and incomplete mitosis after gamma irradiation of kernels of Triticum turgidum ssp. durum L.

Well¹,

Fossey

Booyse

2023

Radiat Environ Biophys

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The study aim was to determine the optimal gamma irradiation dose for mutation breeding in Triticum turgidum ssp. durum L. Root, shoot and seedling growth, as well as the efficiency of energy conversion into growth were determined to examine the growth retardation effects of gamma irradiation that are the result of DNA damage (bridges, ring chromosomes, micronuclei, incomplete mitosis) in Triticum turgidum ssp. durum L. The kernels were irradiated with doses of 50, 150, 250 and 350 Gy using a 60Cobalt gamma-ray source. The kernels were placed in germination paper at 25 °C to grow for a 132 h period for the determination of shoot and root growth and the efficiency of energy conversion into growth. Root tips were collected and fixated over a 47.5 h growth period for the determination of the chromosomal abnormalities and incomplete mitosis. The control differed highly significantly (p < 0.01) from irradiated samples at all doses in root growth and from 250 to 350 Gy samples in shoot growth and the efficiency of energy conversion into growth. There was a highly significant (p < 0.01) increase in the number of bridges and micronuclei between 50 Gy samples and samples irradiated with the higher irradiation doses while 50 Gy samples differed only from 250 and 350 Gy samples regarding ring chromosomes and interphase cells with incomplete mitosis. Root and seedling growth on the one hand and the efficiency of energy conversion into growth on the other were found to be measuring different effects of gamma irradiation on plant growth. The latter was used for the determination of the optimal dose for mutation breeding as 155.52 Gy.

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Comparative study of micronucleus assays and dicentric plus ring chromosomes for dose assessment in particular cases of partial-body exposure

Cited by 10 publications

References 38 publications

New High Throughput Approaches to Detect Partial-body and Neutron Exposures on an Individual Basis

New High Throughput Approaches to Detect Partial-body and Neutron Exposures on an Individual Basis

Derivation of Optimal Experimental Design Methods for Applications in Cytogenetic Biodosimetry

The relationship of the efficiency of energy conversion into growth as an indicator for the determination of the optimal dose for mutation breeding with the appearance of chromosomal abnormalities and incomplete mitosis after gamma irradiation of kernels of Triticum turgidum ssp. durum L.

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