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Interview with Dr Brunhild Halm & Dr Adrian Franke

Posted Tue, Jul, 14,2015

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This author interview is by Dr. Brunhild Halm, of Columbia University and Dr. Adrian Franke, of the University of Hawaii. Dr. Halm and Dr. Franke's full paper, Changes in Whole Blood Gene Expression after Computed Tomography in Children: A Pilot Study, is available for download in Gene Expression to Genetical Genomics.


First please summarise for readers the content of your article.

We evaluated the expression changes of 24 ionizing X-irradiation (IR) candidate genes in young children (3 months to 6 years old) immediately before and 1 hour after they received medically indicated computed tomography (CT) scans. From a literature review, the 24 genes chosen were those most likely to exhibit changes after IR exposure and were also linked to cancer.

How did you come to be involved in your area of study?

Working as a Pediatric Emergency Physician I am confronted with the decision "CT or no CT" on a daily basis. I wanted to get engaged in further research in this area in children since the downsides of radiation affect this age group the most. Plus, since my co-PI, Dr. Adrian Franke works at a Cancer Center as an analytical biochemist with focus on development of biomarkers for detection of cancer early or to prevent it altogether, we both thought that a joint collaboration could lead to valuable translational research and new knowledge in this area.

What was previously known about the topic of your article?

IR from CT has been well documented to elicit a wide variety of detrimental cellular responses including carcinogenesis. CT use for diagnostic medical purposes has risen substantially over the last few decades and the incidence of pediatric CT usage is at present still very high.

Children still undergo significant IR from CT scans for diagnostic medical purposes.

Sometimes a CT is absolutely required and provides valuable information, especially in life threatening situations. However, sometimes it is not needed, for example when parents push unnecessarily for an extra measure of assurance that a child is fine and when physicians practice defensive medicine. This happens often with CT scans in children with minor head injury.

It is very concerning because children have a higher radiosensitivity and longer life expectancy than adults. Plus, if they are exposed to more adult-size radiation doses, which does happen at many adult facilities, the risk of cancer from IR is even more increased.

How has your work in this area advanced understanding of the topic?

The effects of low-dose IR exposure have been the subject of contentious debate among the scientific community for decades. Debate has risen between proponents of the radiation hormesis and linear-no-threshold (LNT) theory, an argument of the beneficial versus detrimental, dose-response effects of IR at low levels.

Much of the data on this subject has been derived from in vitro models (using very high radiation doses) or in vivo adult survivors of Chernobyl and atomic bomb events. Very limited if any data is available from children receiving IR from medically indicated CT scans for diagnostic purposes.

Our pilot data also showed that even relatively low-dose IR relevant to diagnostic CT scans can induce other detrimental DNA changes in vivo in lymphocytes, so called double stranded DNA breaks. This supports the LNT theory that no IR dose should be considered a safe dose.1

Furthermore, we found that CT-derived IR can influence the antioxidant system in vivo and may elicit other detrimental responses on the cellular level.2,3

As a consequence, whenever possible, I now use either ultrasound and magnetic resonance imaging (MRI) for the evaluation of appendicitis in children. Hopefully this approach will spread to others in the near future.

I hope that physicians and also the public are more aware and informed about the side affects of CT scans and that physicians who work with children are questioning and thinking harder before ordering such a test on a child.

What do you regard as being the most important aspect of the results reported in the article?

Even very low IR doses from CT scans in young children were sufficient to elicit expression changes in important radiation-sensitive genes linked to cancer. Thus, when possible, non radiation producing imaging tools such as ultrasound or MRI should be used. If a CT is absolutely indicated child-size radiation doses that follow American College of Radiology's "Imaging Gently" guidelines have to be used in all hospitals.

References
1. Halm BM, Franke AA, Lai JF, et al. γ-H2AX foci are increased in lymphocytes in vivo in young children one hour after very low dose X-irradiation: a pilot study. Pediatr Radiol. 2014;44(10):1310-1317.
2. Halm BM, Lai JF, Morrison CM, et al. In vivo changes in plasma coenzyme Q10, carotenoid, tocopherol, and retinol levels in children after computed tomography. Arch Biochem Biophys. 2014;547:37-43.
3. Halm BM, Franke AA, Lai JF, et al. Pilot Study for the Establishment of Biomarkers for Radiation Damage after Computed Tomography in Children. Hawaii Journal of Medicine and Public Health. March 2015;74(3):112-119.
 

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