Individual response of humans to ionising radiation: governing factors and importance for radiological protection

Applegate, Kimberly E.; Rühm, W.; Wójcik, Andrzej; Bourguignon, M.; Brenner, Alina V.; Hamasaki, Koji; Imai, Takashi; Imaizumi, Misa; Imaoka, Tatsuhiko; Kakinuma, Shizuko; Kamada, Tadashi; Nishimura, Noriyuki; Okonogi, Noriyuki; Ozasa, Kotaro; Rübe, Claudia E.; Sadakane, Atsuko; Sakata, Ritsu; Shimada, Yoshiya; Yoshida, Kengo; Bouffler, Simon

doi:10.1007/s00411-020-00837-y

Cited by 25 publications

(14 citation statements)

References 167 publications

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“…Epidemiological studies have established that radiation exposure is a risk factor for cancer development in humans, and determining the genetic factors that interact with radiation in this context is vital to understanding individuals' responses to radiation [3]; however, screening of genetic polymorphisms related to environmental cancer risk in humans generally requires a massive sample size [7]. In this regard, animal models are useful for studying the role of gene-environment interactions in cancer susceptibility.…”

Section: Discussionmentioning

confidence: 99%

“…These studies have clarified that cancer risk increases with radiation dose in a manner compatible with a linear response, without a threshold, at low doses and low dose rates [2]. They also suggest that the response can be modified by individual factors such as age, sex, and lifestyle factors, including cigarette smoking [3]. Genetic variation is another contributor that governs individual susceptibility to cancer.…”

Section: Introductionmentioning

confidence: 99%

“…Familial cancer exhibits a high probability of inheritance and constitutes approximately 5% of all cancers [4], and greater numbers of genetic polymorphisms are considered to influence cancer risk in a more subtle manner [5]. Although some genetic factors that influence the risk of developing acute tissue reactions after high doses of radiation have been identified, little is known about genetic factors that interact with radiation-induced cancer [3]. Clarification of such interaction would be of benefit when considering radiation use in clinical settings, as well as for the selection of emergency workers and astronauts who will be exposed to relatively high doses of radiation [3].…”

Section: Introductionmentioning

confidence: 99%

“…Although some genetic factors that influence the risk of developing acute tissue reactions after high doses of radiation have been identified, little is known about genetic factors that interact with radiation-induced cancer [3]. Clarification of such interaction would be of benefit when considering radiation use in clinical settings, as well as for the selection of emergency workers and astronauts who will be exposed to relatively high doses of radiation [3].…”

Section: Introductionmentioning

confidence: 99%

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Development of mammary cancer in γ-irradiated F1 hybrids of susceptible Sprague-Dawley and resistant Copenhagen rats, with copy-number losses that pinpoint potential tumor suppressors

et al. 2021

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Copenhagen rats are highly resistant to mammary carcinogenesis, even after treatment with chemical carcinogens and hormones; most studies indicate that this is a dominant genetic trait. To test whether this trait is also dominant after radiation exposure, we characterized the susceptibility of irradiated Copenhagen rats to mammary carcinogenesis, as well as its inheritance, and identified tumor-suppressor genes that, when inactivated or mutated, may contribute to carcinogenesis. To this end, mammary cancer–susceptible Sprague-Dawley rats, resistant Copenhagen rats, and their F1 hybrids were irradiated with 4 Gy of γ-rays, and tumor development was monitored. Copy-number variations and allelic imbalances of genomic DNA were studied using microarrays and PCR analysis of polymorphic markers. Gene expression was assessed by quantitative PCR in normal tissues and induced mammary cancers of F1 rats. Irradiated Copenhagen rats exhibited a very low incidence of mammary cancer. Unexpectedly, this resistance trait did not show dominant inheritance in F1 rats; rather, they exhibited intermediate susceptibility levels (i.e., between those of their parent strains). The susceptibility of irradiated F1 rats to the development of benign mammary tumors (i.e., fibroadenoma and adenoma) was also intermediate. Copy-number losses were frequently observed in chromosome regions 1q52–54 (24%), 2q12–15 (33%), and 3q31–42 (24%), as were focal (38%) and whole (29%) losses of chromosome 5. Some of these chromosomal regions exhibited allelic imbalances. Many cancer-related genes within these regions were downregulated in mammary tumors as compared with normal mammary tissue. Some of the chromosomal losses identified have not been reported previously in chemically induced models, implying a novel mechanism inherent to the irradiated model. Based on these findings, Sprague-Dawley × Copenhagen F1 rats offer a useful model for exploring genes responsible for radiation-induced mammary cancer, which apparently are mainly located in specific regions of chromosomes 1, 2, 3 and 5.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Development of mammary cancer in γ-irradiated F1 hybrids of susceptible Sprague-Dawley and resistant Copenhagen rats, with copy-number losses that pinpoint potential tumor suppressors

et al. 2021

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“…The evidence of an abnormal response to IR in up to 20% of the population is now recognized (Foray et al, 2016;Applegate et al, 2020) and extensive studies are more than ever necessary to address the three possible outcomes due to: (1) radiosensitivty, i. e., complications and side effects of radiotherapy, (2) radiosusceptibility to cancer and (3) radiodegeneration of tissues, e.g., cataract.…”

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confidence: 99%

Plaidoyer pour un soutien fort et durable à la recherche en radiobiologie pour optimiser la radioprotection

Bourguignon¹

2020

Radioprotection

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La radiobiologie (RB) est avec l'épidémiologie et la dosimétrie au coeur de la radioprotection depuis des dizaines d'années (Bourguignon et al., 2017). Puisque les être humains sont exposés de façon continue aux rayonnements ionisants (RI) d'origines variées naturelles et artificielles avec une tendance à l'augmentation des doses notamment aux patients (UNSCEAR, 2008 ; European Dose Datamed II, 2014), il y a un besoin persistant de mise à jour des données de la radiobiologie. Outre cette utilisation défensive de la RB pour la radioprotection, la RB apporte beaucoup plus à la société et en conséquence doit être développée davantage : « La radiobiologie a fait et continue de faire des contributions critiques à la science » (Kirsch et al., 2017). La RB est la connaissance des effets des RI sur la matière vivante (cellules, tissus et organisme) et des mécanismes réactionnels et de défense en ce qui concerne le maintien des structures et des fonctionnements (Tubiana, 2008 ; Hall et Giaccia, 2012). La recherche fondamentale en RB a apporté des avancées significatives sur les mécanismes moléculaires (Ravanat, 2018), cellulaires et tissulaires des effets immédiats des RI et sur les réponses subséquentes retardées. Les cellules ne répondent pas passivement mais activement et réparent de façon dynamique les lésions, notamment celles de l'ADN, avec plus ou moins de succès. En cas d'échec de la réparation de l'ADN, la transformation cellulaire peut conduire à un cancer mais heureusement la mort ultime des cellules protège l'oganisme contre les tranformations cellulaires. Au niveau tissulaire, les cellules communiquent ensemble et échangent des signaux critiques en ce qui concerne l'évolution des cellules et des tissus après irradiation. Cependant trop de morts cellulaires peut conduire à la dégénérescence des tissus et au vieillissement. La compréhension des mécanismes intimes des effets des RI a conduit historiquement à la radiothérapie qui est aujourd'hui une technique majeure de traitement des cancers puisque plus de 50 % des patients cancéreux bénéficient de la radiothérapie avec un taux de succès d'environ 80 %, et ce, à faible coût (10 % du coût total du cancer). Comme inconvénients de ce traitement puissant, des effets secondaires et des complications (Thellier, 2019a, 2019b) ne sont pas si rares alors même qu'il n'y a pas eu d'erreur dans la délivrance de la dose et dans la balistique de l'irradiation (Foray et al., 2016). Les seconds cancers primaires ne sont pas rares et concernent de 8 à 10 % des patients traités (Cosset et al., 2018) et des effets cardiovasculaires sont suspectés et recherchés. La recherche en RB est nécessaire pour comprendre pourquoi des effets secondaires et des complications surviennnent afin de les prévenir et de les traiter efficacement. Une réponse individuelle anormale aux fortes doses de RI, décrite depuis le début du XX e siècle, peut expliquer pour une grande part ces effets secondaires anormaux et ces complications (Foray et al., 2016). De nouveaux paradigmes en radiothérapie, par exe...

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Individual Radiation Sensitivity and Biomarkers: Molecular Radiation Biology

Ainsbury,

Abrantes,

Baatout

et al. 2023

Radiobiology Textbook

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In recent years, scientific understanding of the changes radiation makes to the various tissues of the body has vastly increased. Identification of biological markers of radiation exposure and response has become a wide field with an increasing interest across the radiation research community. This chapter introduces the concepts of individual radiosensitivity, radiosusceptibility, and radiodegeneration, which are the key factors to classify radiation responses. Biomarkers are then introduced, and their key characteristics as well as classification are explained, with a particular focus on those biomarkers which have been identified for use in epidemiological studies of radiation risk—as this is a crucial topic of current interest within radiation protection. Brief information on collection of samples is followed by a detailed presentation of predictive assays in use in different settings including clinical applications with responses assessed chiefly in tissue biopsy or blood samples. The sections toward the end of this chapter then discuss the evidence associated with the relationship between age and separately sex, and radiosensitivity, as well as some genetic syndromes associated with radiosensitivity. The final section of this chapter provides a brief summary of how our current knowledge can further support individual, personalized, uses of radiation, particularly in clinical settings.

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Individual response of humans to ionising radiation: governing factors and importance for radiological protection

Cited by 25 publications

References 167 publications

Development of mammary cancer in γ-irradiated F1 hybrids of susceptible Sprague-Dawley and resistant Copenhagen rats, with copy-number losses that pinpoint potential tumor suppressors

Development of mammary cancer in γ-irradiated F1 hybrids of susceptible Sprague-Dawley and resistant Copenhagen rats, with copy-number losses that pinpoint potential tumor suppressors

Plaidoyer pour un soutien fort et durable à la recherche en radiobiologie pour optimiser la radioprotection

Individual Radiation Sensitivity and Biomarkers: Molecular Radiation Biology

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