Limited evidence for transgenerational chromosomal instability in families with elevated mutation pattern SBS16 in the germline
Purpose The transgenerational effects of preconception parental radiation exposure in humans remain unclear. We assessed genomic integrity in adult children of British nuclear test (NT) veterans—a community that has expressed long-standing concerns about adverse health effects, including in their offspring—to investigate for any constitutional chromosomal abnormalities and/or cytogenetic indicators of genomic instability that might be associated with paternal participation at NT sites. Materials and Methods Peripheral blood samples were obtained from 86 adult children (45 from nuclear test (NT) and 41 control), all born to veterans from the British Army, Royal Air Force, or Royal Navy. Results G-banded karyotyping revealed no constitutional chromosomal abnormalities in any NT sample, including those from families reporting adverse health outcomes. We next assessed for unstable aberrations using conventional Giemsa staining and found some evidence of instability. Specifically, a small subset of NT children (N = 4) showed elevated chromatid aberration frequencies (7.81 ± 4.01 per 100 cells) compared with controls (4.36 ± 0.62; N = 26). To investigate further, we analyzed matched veteran father–child pairs observing a weak association between fathers’ unstable aberration burden and chromatid aberrations in their children, suggesting a potential transgenerational effect. This positive trend was most pronounced in the small group of families (N = 8; 2 control and 6 NT) previously identified as being enriched for mutation signature SBS16 in the germline. Conclusions Although based on a small sample size, this observation warrants further investigation to understand the significance of SBS16, if any, including whether it may serve as a potential transgenerational mutational signature of radiation exposure. Overall, and in the context of health concerns raised by NT families, none of the self-reported health-related variables showed any association with unstable aberration burden in either the veteran fathers or their adult children.
- Research Article
35
- 10.3322/canjclin.48.5.285
- Sep 1, 1998
- CA: A Cancer Journal for Clinicians
Environmental 131I contamination from atmospheric nuclear bomb tests conducted at the NTS from 1951 to 1958 exposed Americans nationwide to a cumulative average dose of 1 to 4 rad to the thyroid gland. By comparison, 10 years of exposure to natural background sources of thyroid radiation results in a cumulative dose of 1 rad. Americans living in certain high-deposition areas received an average cumulative thyroid dose of as much as 16 rad. Individual dose rates vary considerably as a function of age at the time of exposure, site of residence, and dietary habits with respect to milk consumption. The individual cumulative thyroid dose for persons born between 1945 and 1958 may be significantly higher than the reported averages for their locale. The NCI report contains voluminous data tables permitting detailed calculations of individual dose. Additionally, color-coded dose maps allow one to approximate individual dose conveniently. Translation of cumulative thyroid dose attributable to 131I to predictions of increased rates of thyroid cancer appears problematic and is the subject of further study. In contrast to studies of patients receiving external thyroid irradiation, existing studies of patients treated with 131I for diagnostic and therapeutic medical purposes do not document increased rates of thyroid cancer. An Institute of Medicine task force is expected to issue a report on this subject in September 1998. This review also briefly summarizes the evaluation, diagnosis, and treatment of patients with papillary and follicular thyroid cancers. Data from 53,856 patients with thyroid cancer accessioned to the NCDB from 1985 to 1995 document extremely high survival rates for patients in the United States with papillary and follicular thyroid cancer.
- Research Article
5
- 10.1088/1361-6498/ad1743
- Jan 9, 2024
- Journal of radiological protection : official journal of the Society for Radiological Protection
Veterans of the British nuclear testing programme represent a population of ex-military personnel who had the potential to be exposed to ionising radiation through their participation at nuclear testing sites in the 1950s and 1960s. In the intervening years, members of this population have raised concerns about the status of their health and that of their descendants, as a consequence. Radiation dose estimates based on film badge measurements of external dose recorded at the time of the tests suggest any exposure to be limited for the majority of personnel, however, only ∼20% of personnel were monitored and no measurement for internalised exposure are on record. Here, to in-part address families concerns, we assay for chromosomal evidence of historical radiation exposure in a group of aged nuclear test (NT) veterans, using multiplex in situ hybridisation (M-FISH), for comparison with a matched group of veterans who were not present at NT sites. In total, we analysed 9379 and 7698 metaphase cells using M-FISH (24-colour karyotyping) from 48 NT and 38 control veteran samples, representing veteran servicemen from the army, Royal Airforce and Royal Navy. We observed stable and unstable simple- and complex-type chromosome aberrations in both NT and control veterans’ samples, however find no significant difference in yield of any chromosome aberration type between the two cohorts. We do observe higher average frequencies of complex chromosome aberrations in a very small subset of veterans previously identified as having a higher potential for radiation exposure, which may be indicative of internalised contamination to long-lived radionuclides from radiation fallout. By utilising recently published whole genome sequence analysis data of a sub-set of the same family groups, we examined for but found no relationship between paternal chromosome aberration burden, germline mutation frequency and self-reported concerns of adverse health in family members, suggesting that the previously reported health issues by participants in this study are unlikely to be associated with historical radiation exposure. We did observe a small number of families, representing both control and NT cohorts, showing a relationship between paternal chromosome aberrations and germline mutation sub-types which should be explored in future studies. In conclusion, we find no cytogenetic evidence of historical radiation exposure in the cohort of nuclear veterans sampled here, offering reassurance that attendance at NTs sites by the veterans sampled here, was not associated with significant levels of exposure to radiation.
- Research Article
- 10.1080/00396339408442743
- Jun 1, 1994
- Survival
Japan and Korea in the 1990s: From Antagonism to Adjustment By Brian Bridges. Aldershot, Hants: Edward Elgar Publishing Ltd; and Brookfield, VT: Edward Elgar Publishing Company, 1993. 186 pp. £39.95. Indonesian Politics Under Suharto: Order, Development and Pressure for Change By Michael R. J. Vatikiotis. London and New York: Routledge, Politics in Asia Series, 1993. 220pp. £27.50. Asia Pacific in the New World Politics By James C. Hsuing (ed.). Boulder, CO: Lynne Reinner, 1993. 273pp. £15.95. Inside Japan's Defense: Technology, Economics and Strategy by Michael W. Chinworth. McClean, VA: Brassey's (US), 1993. 245pp. $26.00. The Royal Navy ‐ Today and Tomorrow 1993/4 By Admiral of the Fleet Sir Julian Oswald; The British Army ‐ Today and Tomorrow 1993/4 By Major General Makepeace‐Warne; The Royal Air Force ‐ Today and Tomorrow 1993/4 By Air Chief Marshal Sir Michael Armitage. Portsmouth, Hants: Carmichael and Sweet Limited. £75 each; two for £125; three for £150. Strategic Nonviolent Conflict: The Dynamics of People Power in the Twentieth Century by Peter Ackerman and Christopher Kruegler. New York: Praeger Publishers, 1994. 366pp. $22.95. Justice and the Genesis of War By David A. Welch. Cambridge: Cambridge University Press, 1993. 335pp. £35.00. Morality, Prudence and Nuclear Weapons By Steven P. Lee. Cambridge: Cambridge University Press, 1993. 418pp. £45.00. Political Theory, International Relations and the Ethics of Intervention By Ian Forbes and Mark Hoffman (eds). Basingstoke: Macmillan Press, 1993. 249pp. £45.00.
- Book Chapter
- 10.4324/9781315570198-4
- May 23, 2016
Air power at sea operates in the overlapping dimensions of sea and air. Because of that, there was probably bound to be a degree of tension between the protagonists of both. This was partly a question of institutional interests between the Royal Navy and the Royal Air Force and the British Army too, for that matter. But the institutional tension between the Royal Navy and the Royal Air Force was also a question of competing visions of a debate about what air power was for, and these both helped shape, and derived in large measure from, different conceptions of the nature and the needs of British strategy. The Air Ministry, however, had a rather different vision of the future of air power. Like the policy-makers in the Admiralty, the airmen drew lessons from the experience of the First World War and argued that the air could make a decisive contribution to the future security of Britain and its Empire.
- Research Article
17
- 10.1097/hp.0000000000001170
- Oct 1, 2020
- Health physics
The potential health consequences of the Trinity nuclear weapon test of 16 July 1945 at Alamogordo, New Mexico, are challenging to assess. Population data are available for mortality but not for cancer incidence for New Mexico residents for the first 25 y after the test, and the estimates of radiation dose to the nearby population are lower than the cumulative dose received from ubiquitous natural background radiation. Despite the estimates of low population exposures, it is believed by some that cancer rates in counties near the Trinity test site (located in Socorro County) are elevated compared with other locations across the state. Further, there is a concern about adverse pregnancy outcomes and genetic diseases (transgenerational or heritable effects) related to population exposure to fallout radiation. The possibility of an intergenerational effect has long been a concern of exposed populations, e.g., Japanese atomic bomb survivors, survivors of childhood and adolescent cancer, radiation workers, and environmentally exposed groups. In this paper, the likelihood of discernible transgenerational effects is discounted because (1) in all large-scale comprehensive studies of exposed populations, no heritable genetic effects have been demonstrated in children of exposed parents; (2) the distribution of estimated doses from Trinity is much lower than in other studied populations where no transgenerational effects have been observed; and (3) there is no evidence of increased cancer rates among the scientific, military, and professional participants at the Trinity test and at other nuclear weapons tests who received much higher doses than New Mexico residents living downwind of the Trinity site.
- Single Book
- 10.5040/9781350452718
- Jan 1, 2024
Based on a distinguished 35-year career in the RAF as an Air Commodore, Andrew R. Curtis highlights what is wrong with the way defence is managed today, and presents evidence-based proposals to fix it. Defence is failing to deliver. From the ability of the Ministry of Defence (MoD) to develop defence policy, to the single service's - Royal Navy, British Army, and Royal Air Force (RAF) - ability to acquire and maintain military capability, and undertake military operations. This is not a new problem; indeed, ever since the creation of the MoD in 1964, there have been tensions between the department of state and the armed forces over allocations of responsibility, authority and accountability. Concerned with political oversight; the allocation of responsibility, authority, and accountability; administration of people; organisational structures; and policies and processes, Curtis compellingly demonstrates the critical need to reform the management of Defence for the UK’s armed forces to fight and win in the future.
- Research Article
- 10.1056/jw200202260000008
- Jan 1, 2002
- NEJM Journal Watch
Many adverse health effects of nuclear weapons testing (particularly atmospheric testing) have been postulated. One of the greatest fears is that such testing produces germline mutations that could affect not only people exposed to radiation but future generations as well. Of 470 nuclear tests conducted at the …
- Book Chapter
2
- 10.1007/978-3-642-23380-7_5
- Jan 1, 2013
Over the past decade, research efforts have focused on elucidating the cellular and molecular mechanisms of ionizing radiation (IR)-induced effects in eukaryotic and, most importantly, mammalian cells. The primary sources of radiation exposure stem from diagnostic tests, therapeutic treatments, occupational exposures, nuclear tests, nuclear accidents, as well as the growing production of radioactive waste. It is now well accepted that the effects of IR exposure can be noticed far beyond the borders of the directly irradiated tissue. IR can affect neighboring cells, giving rise to a bystander effect. IR effects can also span several generations and influence the progeny of exposed parents, leading to transgenerational effects. Bystander and transgenerational IR effects are linked to the phenomenon of the IR-induced genome instability that manifests itself as chromosome aberrations, gene mutations, late cell death, and aneuploidy. While the occurrence of these phenomena is well documented, the mechanisms that lead to their development are still being defined. Mounting evidence suggests that IR-induced genome instability and bystander and transgenerational effects may be epigenetically mediated. The epigenetic alterations include DNA methylation, histone modification, and RNA-associated silencing. Recent studies show that IR exposure alters epigenetic parameters not only in the directly exposed tissues but also in the distant bystander tissues. Furthermore, transgenerational radiation effects are proposed to be of an epigenetic nature. In this chapter, I will discuss the role of the epigenetics in IR-induced direct responses, as well as in bystander and transgenerational effects.KeywordsBystander effectsDirect effectsDNA methylationEpigeneticsGenome instabilityHistone modificationsMicroRNAsRadiationSmall RNAsTransgenerational genome instability
- Research Article
12
- 10.1038/sj.bdj.2011.937
- Nov 1, 2011
- British Dental Journal
Figures from the British Defence Dental Services reveal that serving personnel in the British Army have a persistently lower level of dental fitness than those in the Royal Navy or the Royal Air Force. No research had been undertaken to ascertain if this reflects the oral health of recruits joining each Service. This study aimed to pilot a process for collecting dental and sociodemographic data from new recruits to each Service and examine the null hypothesis that no differences in dental health existed. Diagnostic criteria were developed, a sample size calculated and data collected at the initial training establishments of each Service. Data for 432 participants were entered into the analysis. Recruits in the Army sample had a significantly greater prevalence of dental decay and greater treatment resource need than either of the other two Services. Army recruits had a mean number of 2.59 (2.08, 3.09) decayed teeth per recruit, compared to 1.93 (1.49, 2.39 p <0.01) in Royal Navy recruits and 1.26 (0.98, 1.53 p <0.001) in Royal Air Force recruits. Among Army recruits 62.7% were from the two most deprived quintiles of the Index of Multiple Deprivation compared to 42.5% of Royal Naval recruits and 36.6% of Royal Air Force recruits. A significant difference in dental health between recruits to each Service does exist and is a likely to be a reflection of the sociodemographic background from which they are drawn.
- Research Article
36
- 10.1353/jmh.2006.0103
- Apr 1, 2006
- The Journal of Military History
"Lack of moral fibre" (LMF), a term introduced by the Royal Air Force in April 1940, was designed to stigmatize aircrew who refused to fly without a medical reason. This article explores the justification for this uncompromising policy, research by neuropsychiatrists into the psychological effects of aerial combat, and their attempts to modify LMF procedures. The reasons why the British Army and Royal Navy did not formally adopt the policy are analyzed in relation to the military context. What happened to airmen subjected to LMF assessment and treatment programs is also discussed in relation to recent British initiatives.
- Single Book
- 10.5040/9798216019909
- Jan 1, 2007
Strategy for Victory: The Development of British Tactical Air Power, 1919-1943examines the nature of the inter-Service crisis between the British Army and the RAF over the provision of effective air support for the army in the Second World War. Material for this book is drawn primarily from the rich collection of documents at the National Archives (UK) and other British archives. The author makes a highly original point that Britain's independent RAF was in fact a disguised blessing for the Army and that the air force's independence was in part a key reason why a successful solution to the army's air support problems was found. The analysis traces why the British army went to war in 1939 without adequate air support and how an effective system of support was organized by the RAF. As such, it is the first scholarly survey of the origins and development of British air support doctrine and practice during the early years of the Second World War. The provision of direct air support was of central importance to the success enjoyed by Anglo-American armies during the latter half of the Second World War. First in North Africa, and later in Italy and North-West Europe, American, British and Empire armies fought most if not all of their battles with the knowledge that they enjoyed unassailable air superiority throughout the battle area. This advantage, however, was the product of a long and bitter dispute between the British Army and the Royal Air Force that began at the end of the First World War and continued virtually unabated until it was resolved in late 1942 and early 1943 when the 2nd Tactical Air Force was created. Battlefield experience and, in particular, success in North Africa, combined with the hard work, wisdom and perseverance of Air Marshals Sir Arthur Tedder and Arthur Coningham, the active co-operation of General Bernard Montgomery, and the political authority of Prime Minister Winston Churchill, produced a uniquely British system that afforded the most comprehensive, effective and flexible air support provided by any air force during the war. The book is divided into two equal parts of five chapters. Part one surveys how the British Army went to war in 1939 without adequate air support, and part two explains how an effective system of air support was organized by the middle years of the war. The analysis traces Britain's earliest experience with aircraft in the Great War 1914-1918, the inter-war period of doctrinal development and inter-Service rivalry, and the major campaigns in France and the Middle East during the first half of the Second World War when the weaknesses in Army-RAF co-operation were first exposed and eventually resolved. As such, it is the first scholarly survey of the origin and development of British air support doctrine and practice during the early years of the Second World War.
- Book Chapter
- 10.1007/978-1-349-21603-1_7
- Jan 1, 1991
Before the Second World War the tasks of the British armed services could be defined relatively easily — the British army was largely engaged overseas as an imperial police force, the Royal Navy was concerned with the protection of Britain's seaborne trade and the defence of British interests in the Mediterranean and the Far East while the Royal Air Force was intended as a deterrent against a German aerial assault on the homeland. Not until 1939 did the government accept unreservedly that in the event of a continental war a British Expeditionary Force should be sent to France.1
- Research Article
10
- 10.1038/s41598-022-14999-w
- Jul 5, 2022
- Scientific reports
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.
- Research Article
1
- 10.1136/military-2022-002309
- Apr 7, 2023
- BMJ Military Health
IntroductionThe main objective was to compare suicide rates and their trends across the three UK Armed forces (Royal Navy, Army and Royal Air Force) from 1900 to 2020. Further objectives...
- Research Article
3
- 10.1136/military-2022-002285
- Feb 1, 2023
- BMJ Military Health
IntroductionThe purpose was to quantify physical performance in men and women during British Army Junior Entry (Army-JE), British Army Standard Entry (Army-SE) and Royal Air Force (RAF) basic training (BT).DesignProspective...
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