Belgium’s Royal Academies of Science and the Arts host symposium entitled:  Health Impact of Pre- and Early Post-natal Irradiation: State-of-the-art. 

On 7 October, a one-day symposium devoted to studying the health effects of pre- and early post-natal irradiation took place at Belgium’s Royal Academies of Science and the Arts. It was a joint initiative of SCK·CEN and the Federal Agency of Nuclear Control. The main objective of this meeting was to assess the latest scientific data in the field of radiation-induced risks resulting from the exposure of embryos and young children to ionising radiation. Leading specialists delivered lectures on the various topics that featured on the symposium agenda. Another objective of the symposium was to discuss current data and their potential implications, as well as the priorities for future research. This part of the symposium consisted of a roundtable discussion between various stakeholders, some of whom work outside of the radiation protection community (journalists, philosophers, legal experts, etc.). The symposium, which sought to present scientifically accurate information whilst at the same time being understandable to an educated but non-specialist audience, attracted more than 120 participants from Belgium and further afield. They included radiologists and other users of ionizing radiation sources, radiobiologists, nurses, technologists, occupational medical doctors, experts in physical control, radio-physicists, regulators, etc.

In the opening lecture, Hanane Derradji, from SCK•CEN, summarised the «classic» risks associated with prenatal irradiation. These can differ, depending on the embryonic stage at which irradiation occurs, and can include embryonic lethality, growth retardation, congenital malformations, mental retardation, leukaemia or cancer.

Paul Jacquet, from the same laboratory, then summarised the associated research that has been carried out  at SCK•CEN, and elsewhere, for more than 30 years. The radiobiology laboratory at SCK•CEN has mainly focused on the influence of the genetic characteristics of the embryo on its sensitivity to developmental anomalies resulting from  exposure to moderate doses of ionising radiation. Particular attention was devoted to the pre-implantation period (10 first days of pregnancy) during which women cannot be aware that they are pregnant. It has long been assumed that during that early period, irradiation could only induce embryonic loss. However, recent research has shown that this “all-or-nothing” assumption is challenged by unexplained exceptions, for example an increased frequency of malformations reported in some mouse strains after irradiation during the first days of pregnancy. The research performed in Mol also included particular mouse strains that carry mutations in various genes involved in essential functions such as DNA repair, cell cycle control or apoptosis. In spite of the negative results obtained in most studies using doses higher than those normally used in radiological procedures, the possibility of radiation-induced congenital anomalies in some particularly sensitive individuals cannot be excluded when irradiation occurs very soon after fertilisation. However, the probability of such events occurring remains very low compared to the «spontaneous» risks associated with pregnancy.

Another area of radiobiological research performed at SCK•CEN concerns the mechanisms of mental retardation associated with prenatal exposure. This area of research was addressed by Rafi Benotmane, the Coordinator of the CEREBRAD Project, in which 11 European research institutes are involved within the framework of the new DoReMi platform. Marten Palme, an economist at Stockholm University, reported on some cognitive effects that were found among Swedish school children who had been exposed in utero to the radioactive cloud after the Chernobyl accident. Exposure occurred between weeks 8 and 25 of pregnancy, i.e. during the “sensitive period” identified by the survey that was carried out on the survivors of the atomic bombings in Hiroshima and Nagasaki. However, in Sweden, the maximal dose to which embryos had been exposed was estimated to be 4 mSv for the first year following the Chernobyl accident, a dose comparable to the annual dose resulting from exposure to natural radioactivity. Of course, the interpretation of such results poses a serious problem for scientists and these results need to be confirmed by other studies performed in other regions of the world that are characterised by an excessive level of radioactivity.

In another very interesting lecture, Wladimir Wertelecki, from South Alabama University, reported on an increase in the frequency of some congenital malformations in the population of Rivne-Polissia, a region of Ukraine strongly contaminated by the Chernobyl accident. The inhabitants of this region remain continuously exposed to abnormally high levels of radioactivity due to their way of life. Mr. Wertelecki was cautious about how to interpret his results, as the observed malformations could also be caused by exposure to other agents like alcohol or dietary insufficiencies of , for example, folic acid (vitamin B9). However, in the latter case, alcohol could not be the only cause of these effects. Mr. Wertelecki also suggested that radiation could possibly act in synergy with one or other of these agents and called for additional collaborative studies to be carried involving this absolutely unique population (contact: genfir3@gmail.com).

Elisabeth Cardis, who was Head of the Radiation Group of  IARC for more than 20 years and is now working at CREAL, (Center for Research in Environmental Epidemiology), in Barcelona, summarised available data on the risks of childhood and adult cancers resulting from in utero exposure. While an increase in childhood cancer cases was observed in a number of epidemiological studies after exposure to low-dose diagnostic X-rays, the extent of such an effect is uncertain. Additionally, an increased risk of cancer in adults was also observed from various studies. But it is still unclear whether the sensitivity of embryos to this effect would be comparable with, higher than or lower than the sensitivity of young children to the same effect.

Hubert Thierens, of Ghent University, reported on an important study that has been carried out involving very young children who had a CT scan. The research team investigated the incidence of double-strand breaks (DSB) in children exposed to X-rays during interventional cardiological procedures. Small volumes of blood were collected before and after the procedure and the number of γ-H2AX foci present in the lymphocytes was observed and compared. The γ-H2AX foci constitute a typical biomarker of radiation-induced DSB. A clear increase in the number of foci due to the interventional X-rays was found in each patient. Moreover, hypersensitivity to this effect was found at the lowest doses and researchers obtained comparable responses after the in vitro irradiation of blood samples. Various elements suggest that this hypersensitivity at very low doses could result from a bystander effect (phenomenon by which non-irradiated cells show the same effects as neighbouring irradiated cells due to the transmission of certain signals by the latter). Importantly, the author concluded that the LNT hypothesis, which is supposed to be conservative, could actually underestimate radiation-induced DNA damage in the low dose range.

Géraldine Thomas, from Imperial College of London, is a member of the team that recently published a very important paper on the «molecular signature» of radiation-induced thyroid cancer in children. This type of cancer constitutes the most obvious health consequence of the Chernobyl accident. It results from an exposure to iodium-131 and essentially affects those people who were children (0-4 years) at the time of exposure to the radioactive cloud. The results available so far suggest that clinical cases of radiation-induced thyroid cancer are similar to those observed in non-irradiated children, born more than one year after the accident occurred. It is interesting to note that the molecular characteristics of these tumours differ from those noted in adults suffering from the same cancer. Generally speaking, molecular analyses do not show differences between the effected children, whatever the origin of the tumour (radiation exposure or not). However, results published very recently by the team indicate an amplification of a small part of chromosome 7, as well as an overexpression of some genes, in particular the CLIP2 gene, in children who had been exposed to the radioactive cloud. This suggests that the latter gene could play an important - and so far unknown - role in radiation-induced cancers.

In the symposium’s final lecture, Simon Bouffler, of the HPA (Health Protection Agency), in the United Kingdom, summarised existing data on the trans-generational effects of radiation. Contrary to what has been observed with animals, no direct data on the hereditary effects of radiation in humans is currently available. Since the 1990s, a number of studies have concentrated on "minisatellites" or "ESTRs" (Expanded Single Tandem Repeats), which are portions of DNA located in non coding regions of genes and are constituted by short sequences repeated a number of times (e.g. GCAATGCAATGCAAT etc.). Changes in the number of repeats have been reported among children of people exposed to radiation, as well as in the progeny of irradiated mice. The results obtained in human beings remain, however, disputed. Trans-generational effects of this type were also reported in mice after in utero exposure. Experimental studies have begun to show that these effects may be mediated by persistent and inheritable changes at the level of gene expression, which are caused by epigenetic modifications of the genome, like DNA methylation and histone acetylation.

The roundtable that followed was moderated by Patrick Smeesters, of the FANC-AFCN, who is also a member of various international scientific committees working in the field of radiation protection. There was a general consensus among symposium participants about the fact that much still remains to be investigated on the effects and mechanisms of ionizing radiation in embryos and young children and that the principle of precaution should continue to prevail as much as possible.

P. Jacquet, PhD
Molecular and Cellular Biology
Institute for Environment, Health and Safety
Belgian Nuclear Research Centre (SCK·CEN)
Boeretang 200
B-2400 Mol
e-mail: pjacquet @sckcen.be