Correspondence: Response to “Evaluating the Cumulative Impact of Ionizing Radiation Exposure With Diagnostic Genetics”

Dear Editor, We appreciate the opportunity to respond to the Letter to the Editor by Professor Wang [1] regarding our article reporting dose estimation curves following in vitro X-ray irradiation using blood from four healthy Korean individuals [2]. Professor Wang raises an important scientific issue in the original research paper, namely, clinical application of cytogenetic dosimetry for low-dose exposure to ionizing radiation (IR) <100 mGy. Except for accidental overexposure, most human exposure to IR, including natural background radiation, diagnostic medical tests, and occupational exposure, is typically at low doses [3]; thus, evaluating risks at this dose range is important. Although the effect of low radiation doses on cancer risk is less well established than that of high doses [3], related studies have recently been published [4, 5]. A study on 262,573 individuals who had been exposed to <100 mGy IR reported that the relative risks of acute myeloid leukemia and acute lymphoblastic leukemia were 2.56 and 5.66, respectively, with an excess risk also apparent for cumulative doses <50 mGy [4]. The report by the Committee on the Biological Effects of Ionizing Radiation concluded that the cancer risk would continue in a linear trend at lower doses of IR, without a threshold, and that the lowest dose has the potential to cause a small increase in risk to humans [5]. However, to date, there is no standard method specifically designed for detecting chromosomal abnormalities following exposure to doses ≤100 mGy, and the accuracy of estimation methods using dose-response curves remains unclear [6]. According to the guidelines of the International Atomic Energy Agency (IAEA) [6], dicentric chromosome (DC) and FISH translocation (TR) assays are typically used following radiation exposure >100 mGy and >250 mGy, respectively. In our study, the curves for DC and TR induced by X-ray irradiation showed good radiation dose responsiveness [2]. However, at doses ≤50 mGy, the increase in the number of DCs observed did not correlate with the radiation dose [2]. This might be due to confounders such as age, smoking, and polymorphisms in DNA repair genes [7]. To reduce the influence of these confounders on the fitted curve, IAEA guidelines recommend that a sufficient number of cells be analyzed, between 3,000 and 5,000 per dose-point [6]. Based on an analysis of more than 5,000 cells for each data point, a prior study reported a strong correlation between radiation dose and DC frequency, even at a low dose of 20 mGy [8]. Another study using multicolor FISH for all 23 homologous pairs found that it served as a good alternative method for improving the identification of chromosome aberrations due to low-dose exposure [9]. In addition to these studies, other approaches for