Lack of transgenerational effects of ionizing radiation exposure from the Chernobyl accident
Genomics of radiation-induced damage
The potential adverse effects of exposures to radioactivity from nuclear accidents can include acute consequences such as radiation sickness, as well as long-term sequelae such as increased risk of cancer. There have been a few studies examining transgenerational risks of radiation exposure but the results have been inconclusive. Morton et al. analyzed papillary thyroid tumors, normal thyroid tissue, and blood from hundreds of survivors of the Chernobyl nuclear accident and compared them against those of unexposed patients. The findings offer insight into the process of radiation-induced carcinogenesis and characteristic patterns of DNA damage associated with environmental radiation exposure. In a separate study, Yeager et al. analyzed the genomes of 130 children and parents from families in which one or both parents had experienced gonadal radiation exposure related to the Chernobyl accident and the children were conceived between 1987 and 2002. Reassuringly, the authors did not find an increase in new germline mutations in this population.
Abstract
Effects of radiation exposure from the Chernobyl nuclear accident remain a topic of interest. We investigated germline de novo mutations (DNMs) in children born to parents employed as cleanup workers or exposed to occupational and environmental ionizing radiation after the accident. Whole-genome sequencing of 130 children (born 1987–2002) and their parents did not reveal an increase in the rates, distributions, or types of DNMs relative to the results of previous studies. We find no elevation in total DNMs, regardless of cumulative preconception gonadal paternal [mean = 365 milligrays (mGy), range = 0 to 4080 mGy] or maternal (mean = 19 mGy, range = 0 to 550 mGy) exposure to ionizing radiation. Thus, we conclude that, over this exposure range, evidence is lacking for a substantial effect on germline DNMs in humans, suggesting minimal impact from transgenerational genetic effects.
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Supplementary Material
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Figs. S1 to S7
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Information & Authors
Information
Published In
Science
Volume 372 • Issue 6543 • 14 May 2021
Pages: 725 - 729
History
Received: 22 December 2020
Accepted: 12 April 2021
22 April 2021
Copyright
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
This is an article distributed under the terms of the Science Journals Default License.
Authors
Funding Information
http://dx.doi.org/10.13039/100000054National Cancer Institute:
http://dx.doi.org/10.13039/100005835American Museum of Natural History:
http://dx.doi.org/10.13039/100012292Gerstner Family Foundation:
RE: Lack of transgenerational effects of ionizing radiation exposure from the Chernobyl accident
Yeager, et al. conclude that there is no evidence for transgenerational effects of radiation in their similarly titled paper. But there are whole sets of evidence missing. Most importantly, the offspring studied were those who survived to adulthood, so all genetic impacts that precluded successful gestation are gone, and survival into adulthood implies fairly normal phenotypic development--so any genetic impacts that caused death in childhood (for instance defects to heart or brain) are likely missing from this data--indicating a huge "sampling bias."
Further, there is no comment about fertility rate in the group studied. Were there pregnancy terminations? Stillbirths? Neonatal deaths? While it is legitimate to report results on the small group studied (105 pairs of parents out of an exposure population several thousands of times larger), it is not legitimate to imply this group represents all the missing data. It does not, and cannot represent that exposed group, let alone "humankind."
The study states subjects were "recruited." Authors give zero indication of how this was done, or how further sampling bias was avoided.
Liquidator and evacuee communities' doses were delivered in a manner different from doses to those living on contaminated land and eating contaminated food over generations, and will provide limited information for these more widespread, and growing, exposure conditions. It would be a mistake to claim that Chernobyl-exposed individuals, even if better represented in the data, would represent all possible transgenerational effects from ionizing radiation.
Oddly, the researchers seem to agree -- as they admit to potential survivor bias -- that further study is needed. Yet the study still resoundingly concludes there are no transgenerational impacts from Chernobyl radiation exposure, a conclusion not warranted by the evidence presented.
Cynthia Folkers, Radiation and Health Hazard Specialist, Beyond Nuclear
Mary Olson, Founder and Director, Gender and Radiation Impact Project
RE: Comment to Yeager M et al. Lack of transgenerational effects of ionizing radiation exposure from the Chernobyl accident. Science 2021 Apr 22 Online ahead of print.
The authors conclude from their results that children of parents exposed by low-dose radiation will not show hereditary effects. They studied de novo mutations (DNM) after Chernobyl in 130 children from 105 mother-father pairs by whole-genome sequencing.
The most sensitive stages of spermatogenesis to radiation – fast dividing spermatocytes, haploid spermatids, and especially the mature spermatozoa - are restricted to a period of 9 weeks before conception (1). Therefore, the current findings of the authors fail to answer the question about hereditary effects in man by Chernobyl exposures, because they consider births which occurred 46 or more weeks after the accident (between 1987-2002, 48 % after 1992). Only a minority of the fathers or no-one was exposed during the sensitive phase. Oogenesis is also a short-time development. It is known from the literature that the stem cells of the germ lines undergo efficient repair after irradiation and the number of stem cell mutations will remain low in cases of low-dose exposure. 130 fathers in the study were considered with a mean dose of 356 mGy und 130 mothers with a mean dose of 19 mGy. Assuming that the exposure occurred predominantly by low LET radiation (Gamma, Beta) and taking the data of the International Commission on Radiological Protection ICRP who estimate a genetic radiation risk of 0.2 % per Sv, this would lead to 0.09 additional cases in the fathers and 0.005 cases in the mothers of the study. Even assuming a relevant underestimation of effects by the ICRP, there was nearly no chance to detect any in the study.
Radiation-induced Down Syndrom is caused during the first or second meiotic division of the oocyte, it occurs very near to the date of conception. A steep increase and cluster were found in Germany 9 months after the Chernobyl event by Sperling et al. (2) and also in Belarus by Lasjuk et al. (3). M.P. Little, who is one of the above mentioned authors, discussed the question of conception near to exposure in a paper of 2013 (4). Why did they not follow their own proposal? It is most relevant in situations with chronical exposure. Holtgrewe et al. found DNMs in children of 10 fathers who were exposed by ionizing radiations during their service in German Radar stations of the military (5). These children suffered from congenital anomalies.
Genetic radiation effects remain a task of protection not only for occupational exposed persons but also because of still increasing medical exposures by CT.
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