γ-H2AX foci as in vivo effect biomarker in children emphasize the importance to minimize x-ray doses in paediatric CT imaging

Abstract

ObjectivesInvestigation of DNA damage induced by CT x-rays in paediatric patients versus patient dose in a multicentre setting.MethodsFrom 51 paediatric patients (median age, 3.8 years) who underwent an abdomen or chest CT examination in one of the five participating radiology departments, blood samples were taken before and shortly after the examination. DNA damage was estimated by scoring γ-H2AX foci in peripheral blood T lymphocytes. Patient-specific organ and tissue doses were calculated with a validated Monte Carlo program. Individual lifetime attributable risks (LAR) for cancer incidence and mortality were estimated according to the BEIR VII risk models.ResultsDespite the low CT doses, a median increase of 0.13 γ-H2AX foci/cell was observed. Plotting the induced γ-H2AX foci versus blood dose indicated a low-dose hypersensitivity, supported also by an in vitro dose–response study. Differences in dose levels between radiology centres were reflected in differences in DNA damage. LAR of cancer mortality for the paediatric chest CT and abdomen CT cohort was 0.08 and 0.13 ‰ respectively.ConclusionCT x-rays induce DNA damage in paediatric patients even at low doses and the level of DNA damage is reduced by application of more effective CT dose reduction techniques and paediatric protocols.Key Points• CT induces a small, significant number of double-strand DNA breaks in children.• More effective CT dose reduction results in less DNA damage.• Risk estimates based on the LNT hypothesis may represent underestimates.

Radiation Induced DNA Double-Strand Breaks in Radiology

“…Fig. 4 Effect of antioxidants on γ-H2AX foci: for combined in-vivo/in-vitro experiments blood samples were obtained from 17 healthy volunteers before, 15,30, 60, 120, 180, and 300 minutes after oral ingestion of a commercially available antioxidant formulation (AO). Samples were irradiated with 10 mGy in-vitro and incubated for 5 minutes.…”

“…This quantity of radiation-induced foci demonstrate a dependence on the dose, which in most in-vitro and in-vivo studies was linear [7, 9,13,23,33]. Individual studies described non-linear relationships [14,15,24]. However, it should be noted that in this working group, the baseline values were higher by a factor of 10 ( • " Table 1).…”

“…However, a non-linear relationship between the number of CT-induced foci and blood dose calculated using Monte Carlo simulation was demonstrated by two studies. One concerned adult patients with thoracic or abdominal CT, the other was described in a recently-published multi-center study by the same research group, involving 51 pediatric patients in 5 centers who had undergone thoracic or abdominal CT [14,15]. A steep rise in the curve was shown in the dose range up to 2 mGy [14] and up to 10 mGy [15]; then the curve flattened.…”

“…Consequently the authors presumed hypersensitivity in the low-dose range. In addition, linear regression analysis demonstrated that the number of induced double-strand breaks per mGy declined with the patients' age [15]. Age-dependent differences in detectable levels of γ-H2AX foci are well-known, but there are little published data in this regard.…”

Time to Terminate LNT: Radiation Regulators Should Adopt LT

“…However, a decade later, studies in pediatric patients obtained data only at 5 minutes [18] or 1 hour [18], after the CT scans, and failed to permit time for repair of the observed and expected initial damage. The authors of the latter study even cite the earlier work of Löbrich et al [17] and note that repair is possible at later intervals post CT.…”