Researchers have observed an increased frequency of chromosomal aberrations in endovascular operators that is likely to be related to occupational radiation.
Speaking in the Prize Session at this year’s European Society for Vascular Surgery (ESVS) annual meeting (28–29 September, Rotterdam, The Netherlands and online), presenter Mohamed Abdelhalim—a doctoral research fellow supervised by Bijan Modarai at King’s College London (London, UK)—conveyed his hope that, with more research, biodosimetry will be used as an adjunct to physical dosimetry in the future.
Modarai and colleagues have previously shown a rise in acute markers of DNA damage in endovascular operators. According to the research team, however, there has been no analysis of biological markers of chronic DNA change to date.
The present research focused in part on dicentric chromosomes, the presenter relayed, noting that these are the “gold standard” for biodosimetry. Such chromosomes are a rare occurrence in the lymphocytes in the normal population, whereas their frequency rises proportionately with radiation exposure, he explained, making them a “very good marker” for radiation damage. Dicentric chromosomes are also associated with malignancy, Abdelhalim added.
The team’s research also considered translocations, which, the presenter clarified, are exchanges of genetic material between two or more chromosomes, some of which are transmissible and therefore have a malignant potential. The final area of research was aneuploidy, which is when a chromosome is lost entirely from a cell, Abdelhalim noted, causing genomic instability and thus having the potential for malignant transformation.
The researchers hypothesised that chronic occupational radiation exposure from endovascular procedures increases the frequency of chromosome aberrations and so aimed to determine the incidence of chromosome aberrations in high-volume endovascular operations.
Abdelhalim summarised the team’s research, which they conducted in collaboration with experts in radiation biology both from Public Health England and Brunel University in London, UK. The team isolated lymphocytes from peripheral blood samples, stimulated mitosis in these lymphocytes, arrested mitosis exactly at the point of metaphase, and then fixed the samples to microscope slides, before separating the samples into two groups: a dicentric assay and a sample analysed with mFISH. “Both of these techniques are incredibly time consuming and labour intensive,” the presenter remarked. Despite this, he conveyed that the team were able to analyse 54,000 cells with the dicentric assay and 2,000 cells with mFISH, which he described as a “completely manual process”.
The team recruited a total of 18 operators for the study, 12 of whom were exposed endovascular operators, with the remaining six being radiation-naïve colorectal surgeons, used as controls. Abdelhalim noted that there were no significant differences between potential confounders between the groups, such as age, years of consultant practice or smoking status. All of the operators in the exposed group did high volumes of endovascular procedures, the speaker added.
“The frequency of dicentric chromosomes is significantly higher in endovascular operators compared with colorectal surgeons,” Abdelhalim revealed. Other key findings were that reciprocal translocation was more common in endovascular operators compared to controls, complex chromosomal arrangements were twice as common, and there was a significantly higher frequency of aneuploidy in the endovascular cohort.
“Something that has never been done before”
“That is excellent and concerning,” panellist Florian Dick (Kantonsspital St Gallen, St Gallen, Switzerland) commented, opening the discussion following Abdelhalim’s presentation. Hence Verhagen (Erasmus University Medical Center, Rotterdam, The Netherlands), another panellist, concurred, emphasising that the research is “very relevant to people like us”.
Panellist Henrik Silesen (Rigshospitalet, University of Copenhagen, Copenhagen, Denmark) was keen to find out if the research is this going to be meaningful for the individual. “We can count the number of minutes [of radiation], but that does not take into account the protection that people are wearing, it does not take into account how well you are protecting yourself. What we are showing here is that, despite our current best practices, there is still biological damage that is being caused,” the presenter replied.
Silesen also asked whether or not the team could have shown differences between operators who are better at saving radiation than other operators. While this was not part of Abdelhalim and colleagues’ research, Dick stressed that this should be an area to focus on in the next decade.
Panellist Jonathan Boyle (Cambridge University Hospitals NHS Trust, Cambridge, UK) wanted to know what was new in the presentation compared to the studies already published by the research group. “Previously, we looked at acute markers, in that, immediately after an EVAR [endovascular aneurysm repair], you have a rise in these markers, and then they normalise completely. So, whether you do one EVAR or 100, it is the same,” Abdelhalim explained. “Here, we have shown what is left behind after years of performing these procedures, and that is something that has never been done before.”
The fact that the markers appear immediately after performing EVAR and then they normalize completely, make me ask: have you seen permanent markers in high volume endovascular operators? This question is crucial for us.
Prof. J C Parodi MD
Have authors of papers related to chromosomal damage in endovascular surgeons noted any evidence for Loss of the Y chromosome (LOY). If so I would register some concern, as mosaic LOY has been reported in patients with abdominal aortic aneurysms (AAA). LOY is under investigation because 1) The ratio of men to women with AAA is high, 2) An immuno-suppressive gene homologous to the female FoxP3 gene resides on the Y Chromosome, and 3) Loss of tolerance because of these factors may explain the high levels of inflammation and immune response seen in clinical AAA disease. I am now among those who surmise that the AAA may be an antigen-driven specific T-cell disease.