Mutation Induction in Humans and Mice: Where Are We Now?

Dubrova, Yuri E.

doi:10.3390/cancers11111708

Cited by 7 publications

(3 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fundamental gaps remain in our understanding of the pattern of mutation induction in humans 1 – 4 . The limited sensitivity of traditional approaches for monitoring newly arising (de novo) mutations (DNMs) in the human germline and their application to the study of the hereditary effects of radiation in humans have often provided conflicting and inconclusive evidence toward the consequences for the children of exposed parents 5 – 8 .…”

Section: Introductionmentioning

confidence: 99%

No evidence of increased mutations in the germline of a group of British nuclear test veterans

Moorhouse

Scholze

Sylvius

et al. 2022

Sci Rep

View full text Add to dashboard Cite

The potential germline effects of radiation exposure to military veterans present at British nuclear tests in Australia and the South Pacific is of considerable interest. We analyzed germline mutations in 60 families of UK military personnel comprising 30 control and 30 nuclear test veterans (NTV). Using whole-genome sequencing we studied the frequency and spectra of de novo mutations to investigate the transgenerational effect of veterans’ (potential) exposure to radiation at nuclear bomb test sites. We find no elevation in total de novo single nucleotide variants, small insertion-deletions, structural variants or clustered mutations among the offspring of nuclear test veterans compared to those of control personnel. We did observe an elevated occurrence of single base substitution mutations within mutation signature SBS16, due to a subset of NTV offspring. The relevance of this elevation to potential exposure of veteran fathers and, future health risks, require further investigation. Overall, we find no evidence of increased mutations in the germline of a group of British nuclear test veterans. ISRCTN Registry 17461668.

show abstract

Section: Introductionmentioning

confidence: 99%

No evidence of increased mutations in the germline of a group of British nuclear test veterans

Moorhouse

Scholze

Sylvius

et al. 2022

Sci Rep

View full text Add to dashboard Cite

show abstract

“…One of the most important deleterious NTE endpoints is genomic instability: persistently elevated rate of mutations and/or genomic rearrangements not only in directly irradiated cells, but also in bystander cells that interacted with the irradiated cells, and in their descendants 11 . This phenomenon, which was particularly well studied in rodents and in some invertebrate animals such as Daphnia , is most likely mediated by epigenetic mechanisms and can be transmitted across generations 31 – 35 . Transgenerational genome destabilization can be caused not only by ionizing radiation, but also by chemical mutagens 34 .…”

Section: Introductionmentioning

confidence: 99%

Quantitative modeling of multigenerational effects of chronic ionizing radiation using targeted and nontargeted effects

Shuryak

Brenner

2021

Sci Rep

View full text Add to dashboard Cite

Stress response signals can propagate between cells damaged by targeted effects (TE) of ionizing radiation (e.g. energy depositions and ionizations in the nucleus) and undamaged “bystander” cells, sometimes over long distances. Their consequences, called non-targeted effects (NTE), can substantially contribute to radiation-induced damage (e.g. cell death, genomic instability, carcinogenesis), particularly at low doses/dose rates (e.g. space exploration, some occupational and accidental exposures). In addition to controlled laboratory experiments, analysis of observational data on wild animal and plant populations from areas contaminated by radionuclides can enhance our understanding of radiation responses because such data span wide ranges of dose rates applied over many generations. Here we used a mechanistically-motivated mathematical model of TE and NTE to analyze published embryonic mortality data for plants (Arabidopsis thaliana) and rodents (Clethrionomys glareolus) from the Chernobyl nuclear power plant accident region. Although these species differed strongly in intrinsic radiosensitivities and post-accident radiation exposure magnitudes, model-based analysis suggested that NTE rather than TE dominated the responses of both organisms to protracted low-dose-rate irradiation. TE were predicted to become dominant only above the highest dose rates in the data. These results support the concept of NTE involvement in radiation-induced health risks from chronic radiation exposures.

show abstract

“…The study of defects at birth in the progeny of individuals exposed to radiation has been traditionally used as a tool to estimate the risk of inheritable effects or radiation due to genome-wide mutations. However, as Dubrova [ 16 ] pointed out, results from both the Hiroshima and Nagasaki survivors’ databases as well as those from patients subjected to radiotherapy failed to provide evidence for such effects. This is, however, at odds with data obtained from irradiating germline cells in rodents, where such effects were highlighted by whole-genome sequencing and attributed to epigenetic mechanisms.…”

mentioning

confidence: 99%