July 13, 2017

expert reaction to study looking at low doses of radiation and blood vessel cells in a dish

New research published in the International Journal of Radiation Biology reports that when endothelial cells are grown in a dish and exposed to radiation, there are molecular changes, and authors suggest this could mean ionizing radiation may have a harmful effect on cardiovascular health.

Prof. Jeremy Pearson, Associate Medical Director at the British Heart Foundation, said:

“The method of study in this paper only uses a single radiation dose, which is equivalent to over 20 times the highest exposure in a single medical scan like a CT or PET scan.  Even with these high levels of radiation being tested, only small changes were noticed in the levels of some proteins in cultured endothelial cells, so the statistical power is low.  In addition, this finding is not ground-breaking and there were no additional measurements to study the health of these cells.

“It is common knowledge that radiation exposure is damaging to tissue and should be kept to a minimum, but there is virtually no evidence that the doses used in medical scans cause permanent damage.  Only where radiation levels are even higher than those tested in this study, such as through repeated radiotherapy for tumours, can we say that detectable cardiovascular damage can be caused.  Therefore, patients should not be concerned and the diagnostic benefits from their scans far outweigh any theoretically possible tissue damage.”

Prof. Dudley Goodhead, Visiting Scientist, MRC Harwell, said:

“This is high-quality research from an excellent laboratory.  The results provide sound evidence that subtle long-term changes to cells that form the inner layer of blood vessels can be caused by a single radiation dose of half a gray of X-rays.  This observation is supportive of several published epidemiological studies that have found a significantly raised risk of cardiovascular disease in people who have received half a gray, or higher, doses to the heart, such as survivors of the atomic bombs in Japan or some radiotherapy patients.  The study is likely to provide insights into the biological mechanisms underlying such risks.

“It should be noted, however, that half a gray should not be regarded as a low dose and no-one would normally receive such a single dose except in some situations of radiotherapy or severe radiation accidents.  Doses from diagnostic X-ray procedures are very much smaller, usually in the range of a few thousandths of a gray; even from a CT scan, doses are only a few hundredths of a gray.  It remains an open question whether accumulation of very many such small doses over a period of time might also impose some cardiovascular risk.”

Dr Barrie Lambert, retired radiation biologist formerly of St Bartholomew’s Hospital Medical College, said:

“It is well established that radiation at high (typically, radiotherapy) doses can damage vascular endothelial cells and some epidemiological studies have linked this with an increased incidence of cardiovascular disease (CVD).  However, the problem with such studies is allowance for other lifestyle causes (confounders) of CVD.

“This paper suggests a mechanism for the radiation induced endothelial dysfunction which is associated with a dose of 0.5 Gy (which is not really a ‘low’ dose in worker or environmental terms) on cultured human coronary artery endothelial cells.  We don’t know whether this in vitro effect can be extrapolated to what happens in the human body, but the power of any radiation epidemiological study is strengthened by data on a radiobiological mechanism, so this is a useful study.”

Dr Tim Chico, Reader in Cardiovascular Medicine / consultant cardiologist, University of Sheffield, said:

“Heart disease starts with damage to the cells lining the arteries (called the endothelium).  Many things damage the endothelium, particularly smoking, high cholesterol, high blood pressure, and diabetes.  However, we have known for a long time that radiation can also damage blood vessels to increase risk of heart disease.  People exposed to radiation after nuclear accidents or after radiation treatment for cancer have an increased risk of heart disease in later years, although thankfully this increase generally seems to be modest.

“The new study shows that when endothelial cells grown in a dish are exposed to X-rays they change their production of many proteins, and this might be one of the reasons radiation increases risk of heart disease.  However, cells grown outside the body are quite different to those in the living organism, so it is hard to be sure that the same thing would happen in ‘real life’.

“This study comes after a recent NICE recommendation to use a test called CT coronary angiography to investigate people with possible heart disease, and this does expose the patient to X-rays.  CT coronary angiography is a very valuable test for detection of heart disease, and I often use it for my own patients.  Obviously, it is important not to expose people to X-rays unnecessarily, but when someone may have serious heart disease, the risks of the X-ray exposure are lower than the risks of not investigating, and most tests that look for heart disease do involve some exposure to radiation.

“It is worth remembering that most of the radiation exposure we all experience comes from the natural environment, rather than medical exposure.”

Prof. Mike Thorne, independent consultant in radiological and environmental science and Director of Mike Thorne and Associates Ltd, said:

“In this study, human arterial endothelial cells were exposed to x-rays to a dose of 0.5 Gy at a dose rate of 0.5 Gy/minute.  This is an acute exposure with the total dose delivered in one minute.  For comparison, a typical CT scan gives an absorbed dose averaged over the whole body of about 0.01 Gy, so the experimental conditions can be envisaged as equivalent to receiving 50 CT scans in rapid succession.  To provide further context, a single acute whole-body dose of about 4 Gy, i.e. eight times that administered in this experiment, would have a fifty percent chance of killing an exposed individual within 30 to 60 days by grossly depressing their bone marrow function.  Thus, the experimental conditions do not correspond to the low dose and low dose rate conditions typically of concern in occupational and public exposure situations, though they are relevant to exposure conditions at Hiroshima and Nagasaki in which adverse effects on the cardiovascular system have been observed.

“With an acute x-ray dose of 0.5 Gy, a significant degree of cell killing and cell sterilisation has typically been observed in other radiobiological studies.  At this dose, about one hundred ion pairs will be created in a typical cell.  Thus, it is not surprising that cells irradiated in this study to this dose exhibit a significant degree of disturbance to their function, including increased production of reactive oxygen species.  What is interesting in this study is that these changes persist for at least 14 days after irradiation.  More generally, this paper is a nice illustration of our increasing ability to explore the detailed response of cells to toxic agents through proteomic analyses of the up- and down-regulation of genes and gene pathways.  Overall, this is a useful contribution to our understanding of the ways in which ionising radiations affect sub-cellular processes, but the degree to which such changes would occur in vivo and their potential significance for the health status of the individual remains to be determined.”

* ‘Proteome analysis of irradiated endothelial cells reveals persistent alteration in protein degradation and the RhoGDI and NO signalling pathways’ by Omid Azimzadeh et al. published in the International Journal of Radiation Biology on Thursday 13 July 2017.

Declared interests

Prof. Dudley Goodhead: “I have no conflicts of interest to declare, except that I am on the editorial board (unpaid of course) of the International Journal of Radiation Biology, which is publishing the paper.  I have had no contact with the journal in respect of this paper.”

Dr Barrie Lambert: “No declarations of interest.”

Dr Tim Chico: “I am a committee member and Treasurer of the British Atherosclerosis Society, a charity established in 1999 to promote UK atherosclerosis research.”

Prof. Mike Thorne: “Dr Mike Thorne has approximately 40 years of experience in operational and environmental radiological protection.  He is an Honorary Fellow of the Society for Radiological Protection and a member of the Editorial Board of the Journal of Radiological Protection.  He is also the Chairman of the Steering Group of the EU-funded COMET Project and an advisor to the IAEA on uranium in the environment.  He is a former president of the Society for Radiological Protection, a former Scientific Secretary to the ICRP, and a former member of ICRP Committee 2.  In the non-nuclear field, Mike has provided advice to the Channel Tunnel Safety Authority and on the safety of developments in the vicinity of chemically hazardous installations.  Mike has appeared as an expert witness in various public inquiries, hearings and civil trials in the UK and the USA, and was a member of the WHO expert group that evaluated US liabilities for compensation in relation to residents of the Rongelap Atoll in the Marshall Islands.  He has published several books (including two volumes on the pharmacodynamics of toxic metals, semi-metals, organic compounds and asbestos) and book chapters, as well as around 100 peer-reviewed journal articles, mainly on the subject of the environmental transport of radioactivity.

Mike has extensive experience in the development and application of biokinetic and pharmacodynamic models for radioactive and non-radioactive contaminants in animals and humans.  He has been involved in various studies on assessing the impacts of chemotoxic materials released from repositories for radioactive wastes.  Within the COMET Project, Mike has been overseeing work on epigenetic mechanisms through which radiation and chemical damage can be propagated, and this has led to a consideration of techniques for assessing synergistic effects between chemotoxic and radiotoxic materials.”