Establishing a Reference Dose-Response Calibration Curve for Dicentric Chromosome Aberrations to Assess Accidental Radiation Exposure in Saudi Arabia

Abstract

In cases of nuclear and radiological accidents, public health and emergency response need to assess the magnitude of radiation exposure regardless of whether they arise from disaster, negligence, or deliberate act. Here we report the establishment of a national reference dose-response calibration curve (DRCC) for dicentric chromosome (DC), prerequisite to assess radiation doses received in accidental exposures. Peripheral blood samples were collected from 10 volunteers (aged 20-40 years, median = 29 years) of both sexes (three females and seven males). Blood samples, cytogenetic preparation, and analysis followed the International Atomic Energy Agency EPR-Biodosimetry 2011 report. Irradiations were performed using 320 kVp X-rays. Metafer system was used for automated and assisted (elimination of false-positives and inclusion of true-positives) metaphases findings and DC scoring. DC yields were fit to a linear-quadratic model. Results of the assisted DRCC showed some variations among individuals that were not statistically significant (homogeneity test, P = 0.66). There was no effect of age or sex (P > 0.05). To obtain representative national DRCC, data of all volunteers were pooled together and analyzed. The fitted parameters of the radiation-induced DC curve were as follows: Y = 0.0020 (±0.0002) + 0.0369 (±0.0019) ^*D + 0.0689 (±0.0009) ^*D². The high significance of the fitted coefficients (z-test, P < 0.0001), along with the close to 1.0 p-value of the Poisson-based goodness of fit (χ² = 3.51, degrees of freedom = 7, P = 0.83), indicated excellent fitting with no trend toward lack of fit. The curve was in the middle range of DRCCs published in other populations. The automated DRCC over and under estimated DCs at low (<1 Gy) and high (>2 Gy) doses, respectively, with a significant lack of goodness of fit (P < 0.0001). In conclusion, we have established the reference DRCC for DCs induced by 320 kVp X-rays. There was no effect of age or sex in this cohort of 10 young adults. Although the calibration curve obtained by the automated (unsupervised) scoring misrepresented dicentric yields at low and high doses, it can potentially be useful for triage mode to segregate between false-positive and near 2-Gy exposures from seriously irradiated individuals who require hospitalization.

Keywords: Dicentric Chromosome (DC); Dicentric chromosome assay (DCA); biodosimetry; chromosome aberration; dose-response curve; radiation emergency preparedness; radiation exposure.

Figure 1

Representative examples of Metafer5 interface screenshot (upper) along with normal metaphase, and metaphases with dicentrics (DCs; arrows) and other observed aberrations, such as acentric fragments (Ac) and ring (R) (lower). The average number of dicentric per metaphase (i.e., DC yield) and the appearance of other aberations increase with increasing radiation dose received by the lymphocytes in the blood samples.

Figure 2

Individuals' linear–quadratic dose–response curves (solid lines) for dicentric chromosome aberrations induced by 320 kVp X-rays in lymphocytes derived from 10 Saudi volunteers. Data points represent the yield of dicentric per metaphase scored using assisted (supervised) mode. Dashed lines indicate the 95% confidence limits calculated assuming Poisson distribution of the dicentrics data. Error bars represent the standard errors of the dicentric yield.

Figure 3

Left: Comparison of the individuals' dose–response curves for dicentric chromosome aberrations induced by 320 kVp X-rays in lymphocytes derived from 10 Saudi volunteers. Right: The reference dose–response calibration curve (solid line) generated from the pooled data of the 10 volunteers. Dashed lines indicate the 95% confidence limits calculated assuming Poisson distribution of the dicentrics data. Error bars represent the standard errors of the dicentric yield.

Figure 4

The effect of age (left) and sex (right) on the dose–response curves (solid lines) of dicentric chromosome aberrations in 10 Saudi volunteers. Dashed lines are the 95% confidence limits calculated assuming Poisson distribution of the dicentrics data. Error bars represent the standard errors of the dicentric yield.

Figure 5

Assisted (supervised) and automated (unsupervised) reference dose–response calibration curves (solid lines) for dicentric chromosome aberrations induced by 320 kVp X-rays in lymphocytes derived from 10 Saudi volunteers. Data points represent the yield of dicentric per metaphase scored. Dashed lines indicate the 95% confidence limits calculated assuming Poisson distribution of the dicentrics data. Error bars represent the standard errors of the dicentric yield.

Figure 6

Comparison of the published dose–response calibration curves of dicentric chromosome aberrations induced by X-rays: 1. Germany, 90 kVp at 0.1 Gy/min (in (26); 2. Italy, 100 kVp at 1 Gy/min (30); 3. Canada, 250 kVp (29); 4. Preliminary dose–response curve in Saudi Arabia, 320 kVp at 1.33 Gy/min (20); 5. Germany, 250 kVp at 1 Gy/min (in (26); 6. The Netherlands, 100 kVp at 0.4 Gy/min (31); 7. Saudi Arabia, this study, 320 kVp at 1 Gy/min; 8. England, 250 kVp (28); 9. Germany, 240 kVp at 1 Gy/min (26); 10. Serbia, 250 kVp (33); 11. Germany, 220 kVp at 0.5 Gy/min (34); 12. Spain, 180 kVp at 0.27 Gy/min (in (26); 13. United States, 250 kVp at 1 Gy/min (32); 14. Indonesia, 122/250 kVp at 0.17 Gy/min (19).