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Ionizing radiation is a known inducer of cytogenetic abnormalities including chromosome aberrations and micronuclei in human peripheral lymphocytes. Accurate dose estimates can be made by biological dosimetry to predict acute radiation syndrome(ARS) within days after a radiation accident or a malicious act involving radiation[1-2]. Timely information on dose is quintessential for the medical management of acutely irradiated personnel. Chromosome aberration is widely used as a sensitive biomarker for evaluating the damage caused by acute radiation exposure[3-4]. Specifically, dicentric chromosomes (dic) and rings (r) are standard markers for radiation exposure[5-6]. Moreover, cytokinesis-blocked micronuclei (CBMN) supplement chromosome aberration analysis[7]. A single biological assay cannot fully evaluate biodosimetry requirements in complex exposure scenarios. Recent studies are currently focused on searching for new biomarkers for radiation damage evaluation and dose estimation. Research on multifaceted methods for biological assessments seem to aid in clinical management of radiation accident victims[8].
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Interestingly, Gupta et al.[13] described blood bio-markers in a 60Co radiation accident in India. They detected chromosome aberration, γ-H2AX, and other blood parameters including total leukocyte counts and platelet counts in the victims. This multi-parametric approach confirmed that individuals exposed, providing valuable information for assessment and management of victims for radiation accidents in future. Work of Gupta et al. included valuable data on blood parameters, dicentrics, γ-H2AX, and clinical symptoms in victims exposed accidentally[13].
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Physicians should determine leukocyte, platelet, and haemoglobin levels daily, especially after hospital admission. Calculating daily blood cell depletion kinetics is essential for medical management of radiation victims. For scientific interest purposes, the laboratory should obtain blood samples at frequent intervals to monitor changes in differential white cells.
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For the cytogenetic assay, venipuncture blood samples should be taken within four weeks after exposure. After this period, aberration yields appear to decline, causing greater uncertainty in radiation dose estimation[6]. We obtained blood samples 4 and 56 days after a 60Co accident in China, for three victims, which showed that sampling time for dose estimation using chromosome aberration is no more than 56 days after exposure[14] (Table 1). Thus, radiation dose estimation for Indian victims is acceptable after 30 days after the incidence.
Subject Sex Age
(years)4 days post exposure 56 days post exposure Metaphase studied
(dic+r)Dose, Gy
(95% CI)Metaphase studied
(dic+r)Dose, Gy
(95% CI)A F 38 40(79) 5.09
(4.46-5.64)150(357) 5.61
(5.24-5.95)B M 8 217(113) 2.49
(2.23-2.74)300(154) 2.48
(2.26-2.68)C M 37 334(188) 2.61
(2.40-2.80)300(178) 2.68
(2.46-2.89)Notes: dic+r: dicentric chromosomes and rings; CI: confidence intervals. Table 1. Chromosome aberration analysis and biological dose estimation 4 and 56 days post exposure
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Results of chromosome aberration for patient 4 (P4) in Table 1 were inconsistent with those in Fig.3 of Cupta et al.[13]. Two dicentrics in 43 metaphase lymphocytes of P4 are recorded in Table 1, but approximately 20 dicentrics were found according to dicentric frequency 30 days after exposure. This discrepancy may be due to dose estimation differences between dicentric frequencies for P4. Based on data in Table 1(Gupta et al.)[13], we estimated the dose of five victims using the dose-response curve[14]of γ ray-induced chromosome aberration(Table 2):
Subject Metaphase studied Dicentrics Mean dose, Gy(95% CI) P1 35 2 0.69(0.00-1.16) P2 30 2 0.76(0.00-1.27) P3 62 1 0.29(0.00-0.61) P4 43 2 0.61(0.00-1.03) 43 20a 2.35(1.89-2.73) P5 57 2 0.50(0.00-0.87) Note: a: estimation according to frequency of dicentric in Fig.3 by Gupta et al.; CI: confidence interval. Table 2. Biological dose estimation based on Gupta et al.(30 days post exposure)
$Y 1=3.4967 \times 10^{-2} D+6.9490\;7 \times 10^{-2} D^{2} $ Where Y1 denotes dic+r number in each lymphocyte and D is the radiation dose(Gy). The dose range is 0.5 Gy to 5.0 Gy. The mean radiation dose and its 95% confidence interval were thus calculated for each subject based on Equation(1).
According to estimated doses in Table 2, five victims may suffer from mild acute radiation sickness (ARS), but P4 may suffer from moderate ARS if 20 dicentrics is the correct chromosome aberration score. On the 30th day after the accident, the total leukocyte counts in patients P1, P2, P3 and P5 ranged from 3100-5600/mm[3], but only 30-62 metaphase lymphocytes were found in chromosome aberration analysis, which may be the reason for the failed radiation dose estimation.
Additionally, a dicentric was not marked in Fig.4 of Gupta et al.[13](Fig. 1). Reliable scoring of chromosome aberrationwas a dependable means for dose estimation and offers valuable information for treatment of ARS patients; its omission might result in the underevaluation of radiation dose.
Learning From Biomarkers in Victims Acci-dentally Exposed to Ionizing Radiation
Learning From Biomarkers in Victims Acci-dentally Exposed to Ionizing Radiation
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关键词:
- Radiation, ionizing /
- Accident /
- Chromosome aberration /
- Lessons
Abstract: Biomarkers, such as chromosome aberration and micronuclei assays, prove to be reliable for facilitating clinical diagnosis in radiation accidents. In a radiation accident in India, chromosomal aberration, γ-H2AX, as well as other blood markers, were detected in accidentally exposed victims. This multi-parametric approach aided in confirming that individuals had been exposed by ionizing radiation. However, doses were impossible to estimate because of a 30-day delay in accident awareness. Exposure dose for victims was estimated using a dose-response curve previously established. Dose estimation, blood cell depletion kinetics, and no appearance of prodromal symptoms suggested that doses of exposure were low. Hematologic investigation, sampling time, and chromosome aberration scoring were all proposed according to data from the victims exposed to 60Co. Finally, knowledge regarding chromosome aberration analysis and the importance of international co-operation and assistance should be shared from this accident.-
Key words:
- Radiation, ionizing /
- Accident /
- Chromosome aberration /
- Lessons
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Table 1. Chromosome aberration analysis and biological dose estimation 4 and 56 days post exposure
Subject Sex Age
(years)4 days post exposure 56 days post exposure Metaphase studied
(dic+r)Dose, Gy
(95% CI)Metaphase studied
(dic+r)Dose, Gy
(95% CI)A F 38 40(79) 5.09
(4.46-5.64)150(357) 5.61
(5.24-5.95)B M 8 217(113) 2.49
(2.23-2.74)300(154) 2.48
(2.26-2.68)C M 37 334(188) 2.61
(2.40-2.80)300(178) 2.68
(2.46-2.89)Notes: dic+r: dicentric chromosomes and rings; CI: confidence intervals. Table 2. Biological dose estimation based on Gupta et al.(30 days post exposure)
Subject Metaphase studied Dicentrics Mean dose, Gy(95% CI) P1 35 2 0.69(0.00-1.16) P2 30 2 0.76(0.00-1.27) P3 62 1 0.29(0.00-0.61) P4 43 2 0.61(0.00-1.03) 43 20a 2.35(1.89-2.73) P5 57 2 0.50(0.00-0.87) Note: a: estimation according to frequency of dicentric in Fig.3 by Gupta et al.; CI: confidence interval. -
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