Evidence for transgenerational effects following exposure to ionising radiation. A briefing note prepared by by a subgroup of the Advisory Group on Ionising Radiation (original) (raw)
Related papers
PLoS ONE, 2012
The non-targeted effects of human exposure to ionising radiation, including transgenerational instability manifesting in the children of irradiated parents, remains poorly understood. Employing a mouse model, we have analysed whether low-dose acute or low-dose-rate chronic paternal c-irradiation can destabilise the genomes of their first-generation offspring. Using single-molecule PCR, the frequency of mutation at the mouse expanded simple tandem repeat (ESTR) locus Ms6-hm was established in DNA samples extracted from sperm of directly exposed BALB/c male mice, as well as from sperm and the brain of their first-generation offspring. For acute c-irradiation from 10-100 cGy a linear dose-response for ESTR mutation induction was found in the germ line of directly exposed mice, with a doubling dose of 57 cGy. The mutagenicity of acute exposure to 100 cGy was more pronounced than that for chronic low-dose-rate irradiation. The analysis of transgenerational effects of paternal irradiation revealed that ESTR mutation frequencies were equally elevated in the germ line (sperm) and brain of the offspring of fathers exposed to 50 and 100 cGy of acute c-rays. In contrast, neither paternal acute irradiation at lower doses (10-25 cGy), nor low-dose-rate exposure to 100 cGy affected stability of their offspring. Our data imply that the manifestation of transgenerational instability is triggered by a threshold dose of acute paternal irradiation. The results of our study also suggest that most doses of human exposure to ionising radiation, including radiotherapy regimens, may be unlikely to result in transgenerational instability in the offspring children of irradiated fathers.
Genetic Radiation Risks-A Neglected Topic in the Low Dose Dabate
Environmental Health and Toxicology, 2016
The United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) as well as the International Commission on Radiological Protection (ICRP) present very low risk factor for hereditary diseases in humans based on experiments in mice. The claim is based on reportedly absent genetic effects in the acute exposed Japanese A-bomb survivors. We question the safety of these assumptions and have made a compilation of findings about early deaths, congenital malformations, Down´s syndrome, cancer and other genetic effects observed in humans after the exposure of parents. We review evidence from occupationally exposed groups, from studies in populations exposed to Chernobyl fallout and from the descendants of liquidators and nuclear test veterans. Nearly all types of hereditary defects were found at very low doses. We discuss this clash between risk models and observation on the basis of knowledge of biological mechanisms and the effect of assumptions about linear relations between dose and end point in neonatal epidemiology. Using data from Chernobyl effects we derive an Excess Relative Risk for all Malformations of 1.0 per 10mSv cumulative exposure to fission product contamination. The dose response is non-linear "hogs-back" or biphasic and saturates at doses above 10mSv
Lack of transgenerational effects of ionizing radiation exposure from the Chernobyl accident
Science, 2021
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.
Radiation-induced transgenerational instability
Oncogene, 2003
To date, the analysis of mutation induction has provided an irrefutable evidence for an elevated germline mutation rate in the parents directly exposed to ionizing radiation and a number of chemical mutagens. However, the results of numerous publications suggest that radiation may also have an indirect effect on genome stability, which is transmitted through the germ line of irradiated parents to their offspring. This review describes the phenomenon of transgenerational instability and focuses on the data showing increased cancer incidence and elevated mutation rates in the germ line and somatic tissues of the offspring of irradiated parents. The possible mechanisms of transgenerational instability are also discussed.
Genetic Radiation Risks: a neglected topic in the low dose debate
Objectives: To investigate the accuracy and scientific validity of the current very low risk factor for hereditary diseases in humans following exposures to ionizing radiation adopted by the United Nations Scientific Committee on the Effects of Atomic Radiation and the International Commission on Radiological Protection. The value is based on experiments on mice due to reportedly absent effects in the Japanese atomic bomb (Abomb) survivors. Methods: To review the published evidence for heritable effects after ionising radiation exposures particularly, but not restricted to, populations exposed to contamination from the Chernobyl accident and from atmospheric nuclear test fallout. To make a compilation of findings about early deaths, congenital malformations, Down’s syndrome, cancer and other genetic effects observed in humans after the exposure of the parents. To also examine more closely the evidence from the Japanese A-bomb epidemiology and discuss its scientific validity. Results Nearly all types of hereditary defects were found at doses as low as one to 10 mSv. We discuss the clash between the current risk model and these observations on the basis of biological mechanism and assumptions about linear relationships between dose and effect in neonatal and foetal epidemiology. The evidence supports a dose response relationship which is non-linear and is either biphasic or supralinear (hogs-back) and largely either saturates or falls above 10 mSv. Conclusions: We conclude that the current risk model for heritable effects of radiation is unsafe. The dose response relationship is non-linear with the greatest effects at the lowest doses. Using Chernobyl data we derive an excess relative risk for all malformations of 1.0 per 10 mSv cumulative dose. The safety of the Japanese A-bomb epidemiology is argued to be both scientifically and philosophically questionable owing to errors in the choice of control groups, omission of internal exposure effects and assumptions about linear dose response.
Evaluation of radiation risk: cytogenetic and molecular markers of low-dose radiation effects
For last 15 years, we have investigated low-dose radiation genetic effects on human populations affected by the Chernobyl accident. Cytogenetic longitudinal investigations showed that radiation markers for cleanup workers remained at an elevated level and had a trend to grow up with time. A dynamic profile of the amount of aberrations confirms that this group has symptoms of the genomic instability state formation. This situation correlated with the incidence of morbidity. The state of genomic instability correlates with accumulation in cleanup workers blood clastogenic factors, which are responsible for increased genomic instability. As a model, we used keratinocyte human line with blocked first check point of cell cycle. The same situation took place for gene mutations (investigated by T-cell receptor [TCR] test) and mitochondrial "common deletion" frequencies (in situ polymerase chain reaction [PCR]) in cleanup workers as for other groups in the affected population (for children, especially). The outcomes of biology dose reconstruction will be presented. Results of longitudinal investigations confirm that cytogenetic and molecular effects of irradiation can be fixed even 20 years after the Chernobyl accident.
Multisite de novo mutations in human offspring after paternal exposure to ionizing radiation
Scientific reports, 2018
A genome-wide evaluation of the effects of ionizing radiation on mutation induction in the mouse germline has identified multisite de novo mutations (MSDNs) as marker for previous exposure. Here we present the results of a small pilot study of whole genome sequencing in offspring of soldiers who served in radar units on weapon systems that were emitting high-frequency radiation. We found cases of exceptionally high MSDN rates as well as an increased mean in our cohort: While a MSDN mutation is detected in average in 1 out of 5 offspring of unexposed controls, we observed 12 MSDNs in altogether 18 offspring, including a family with 6 MSDNs in 3 offspring. Moreover, we found two translocations, also resulting from neighboring mutations. Our findings indicate that MSDNs might be suited in principle for the assessment of DNA damage from ionizing radiation also in humans. However, as exact person-related dose values in risk groups are usually not available, the interpretation of MSDNs in...
Relevance of the Chernobyl Research for the Evaluation of Genetic Radiation Risks in Humans
Genetics, Evolution and Radiation, 2016
The committee of the United Nations for the evaluation of radiation effects UNSCEAR up to now has derived a very low risk for hereditary diseases from experiments in mice. They claim that there are no human data to refer on, and missing effects in the Japanese A-bomb survivors are erroneously generalized for cases of chronic exposures. Vladimir A. Shevchenko criticized their estimates already soon after the Chernobyl accident. He stated that the main contribution of possible effects as many congenital malformations and all polygenic diseases were left out. He also demanded that the estimates must include the following generations until equilibrium of heritable defects is reached, while the committee considers only the first generation. Shevchenko referred to the rising rates in the Belarussian central registry for congenital anomalies after 1986 and emphasized the importance of biological dosimetry by cytogenetic analysis in order to receive realistic information about the population exposure. We made a compilation of findings about early deaths, congenital malformations, Down´s syndrome, cancer and other effects, which were observed in humans after exposure of parents. Few of them are available from occupationally exposed collectives, much information can be drawn from studies in populations exposed by Chernobyl fallout and from the descendants of liquidators. Nearly all types of hereditary defects were found, which are to be expected according to our general knowledge about it. It can clearly be shown that the official risk estimates are much too low.
Genetic effects of low-dose radiation
Journal of Environmental and Occupational Science
The last update: https://www.researchgate.net/publication/361227022\_Low-dose\_ionizing\_radiation\_Overestimation\_of\_effects\_and\_overtreatment RELATED ARTICLES: https://pubmed.ncbi.nlm.nih.gov/23000512/ https://www.researchgate.net/publication/324156411\_Hormesis\_and\_radiation\_safety\_norms\_Comments\_for\_an\_update BOOK: https://www.researchgate.net/publication/331320912\_The\_overestimation\_of\_medical\_consequences\_of\_low-dose\_exposure\_to\_ionizing\_radiation RUSSIAN: https://www.researchgate.net/publication/275659766\_O\_radiacionno-inducirovannyh\_mutaciah https://www.researchgate.net/publication/316316321\_O\_perestrojkah\_RETPTC\_v\_rake\_sitovidnoj\_zelezy\_posle\_avarii\_na\_CAES\_RETPTC\_rearrangements\_in\_thyroid\_carcinoma\_after\_the\_Chernobyl\_accident
The long-term genetic effects of maternal irradiation remain poorly understood. To establish the effects of radiation exposure on mutation induction in the germline of directly exposed females and the possibility of transgenerational effects in their non-exposed offspring, adult female BALB/c and CBA/Ca mice were given 1 Gy of acute X-rays and mated with control males. The frequency of mutation at expanded simple tandem repeat (ESTR) loci in the germline of directly exposed females did not differ from that of controls. Using a single-molecule PCR approach, ESTR mutation frequency was also established for both germline and somatic tissues in the first-generation offspring of irradiated parents. While the frequency of ESTR mutation in the offspring of irradiated males was significantly elevated, maternal irradiation did not affect stability in their F 1 offspring. Considering these data and the results of our previous study, we propose that, in sharp contrast to paternal exposure to ionising radiation, the transgenerational effects of maternal high-dose acute irradiation are likely to be negligible.