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1.
Trends Genet ; 37(9): 830-845, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34088512

RESUMO

A growing number of known species possess a remarkable characteristic - extreme resistance to the effects of ionizing radiation (IR). This review examines our current understanding of how organisms can adapt to and survive exposure to IR, one of the most toxic stressors known. The study of natural extremophiles such as Deinococcus radiodurans has revealed much. However, the evolution of Deinococcus was not driven by IR. Another approach, pioneered by Evelyn Witkin in 1946, is to utilize experimental evolution. Contributions to the IR-resistance phenotype affect multiple aspects of cell physiology, including DNA repair, removal of reactive oxygen species, the structure and packaging of DNA and the cell itself, and repair of iron-sulfur centers. Based on progress to date, we overview the diversity of mechanisms that can contribute to biological IR resistance arising as a result of either natural or experimental evolution.


Assuntos
Bactérias/efeitos da radiação , Reparo do DNA , Extremófilos/fisiologia , Extremófilos/efeitos da radiação , Radiogenética/métodos , Radiação de Fundo , Fenômenos Fisiológicos Bacterianos , Deinococcus/fisiologia , Deinococcus/efeitos da radiação , Radiação Ionizante
2.
Nucleic Acids Res ; 48(19): e111, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33010172

RESUMO

Ionizing radiation (IR) is environmentally prevalent and, depending on dose and linear energy transfer (LET), can elicit serious health effects by damaging DNA. Relative to low LET photon radiation (X-rays, gamma rays), higher LET particle radiation produces more disease causing, complex DNA damage that is substantially more challenging to resolve quickly or accurately. Despite the majority of human lifetime IR exposure involving long-term, repetitive, low doses of high LET alpha particles (e.g. radon gas inhalation), technological limitations to deliver alpha particles in the laboratory conveniently, repeatedly, over a prolonged period, in low doses and in an affordable, high-throughput manner have constrained DNA damage and repair research on this topic. To resolve this, we developed an inexpensive, high capacity, 96-well plate-compatible alpha particle irradiator capable of delivering adjustable, low mGy/s particle radiation doses in multiple model systems and on the benchtop of a standard laboratory. The system enables monitoring alpha particle effects on DNA damage repair and signalling, genome stability pathways, oxidative stress, cell cycle phase distribution, cell viability and clonogenic survival using numerous microscopy-based and physical techniques. Most importantly, this method is foundational for high-throughput genetic screening and small molecule testing in mammalian and yeast cells.


Assuntos
Partículas alfa/efeitos adversos , Dano ao DNA/efeitos da radiação , Reparo do DNA/efeitos da radiação , Instabilidade Genômica/efeitos da radiação , Radiogenética/instrumentação , Células A549 , Ciclo Celular/efeitos da radiação , Células HeLa , Humanos , Estresse Oxidativo/efeitos da radiação , Saccharomyces cerevisiae , Transdução de Sinais/efeitos da radiação
3.
Chem Biol Interact ; 310: 108736, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31278902

RESUMO

The linear non-threshold (LNT) dose response model for cancer risk assessment has been a controversial concept since its initial proposal during the 1930s. It was long advocated by the radiation genetics community in the 1950s, some two decades prior to being generally adopted within the chemical toxicology community. This paper explores possible reasons for such major differences in the acceptance of LNT for cancer risk assessment by these two key groups of scientists.


Assuntos
Modelos Lineares , Neoplasias/etiologia , Radiação Ionizante , Medição de Risco/normas , United States Environmental Protection Agency/normas , Relação Dose-Resposta à Radiação , Humanos , Radiogenética/normas , Toxicologia/normas , Estados Unidos
4.
Strahlenther Onkol ; 194(8): 780-786, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29774397

RESUMO

PURPOSE: This systematic review evaluates the completeness of dosimetric features and their inclusion as covariates in genetic-toxicity association studies. MATERIALS AND METHODS: Original research studies associating genetic features and normal tissue complications following radiotherapy were identified from PubMed. The use of dosimetric data was determined by mining the statement of prescription dose, dose fractionation, target volume selection or arrangement and dose distribution. The consideration of the dosimetric data as covariates was based on the statement mentioned in the statistical analysis section. The significance of these covariates was extracted from the results section. Descriptive analyses were performed to determine their completeness and inclusion as covariates. RESULTS: A total of 174 studies were found to satisfy the inclusion criteria. Studies published ≥2010 showed increased use of dose distribution information (p = 0.07). 33% of studies did not include any dose features in the analysis of gene-toxicity associations. Only 29% included dose distribution features as covariates and reported the results. 59% of studies which included dose distribution features found significant associations to toxicity. CONCLUSION: A large proportion of studies on the correlation of genetic markers with radiotherapy-related side effects considered no dosimetric parameters. Significance of dose distribution features was found in more than half of the studies including these features, emphasizing their importance. Completeness of radiation-specific clinical data may have increased in recent years which may improve gene-toxicity association studies.


Assuntos
Coleta de Dados/métodos , Relação Dose-Resposta à Radiação , Radiogenética/métodos , Lesões por Radiação/genética , Radiometria/métodos , Marcadores Genéticos/genética , Marcadores Genéticos/efeitos da radiação , Testes Genéticos , Humanos , Radioterapia/efeitos adversos , Estatística como Assunto
5.
Radiología (Madr., Ed. impr.) ; 60(supl.1): 23-35, mayo 2018. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-175335

RESUMO

La resonancia magnética (RM) integra en los protocolos multiparamétricos clínicos actuales información estructural, fisiológica y metabólica del cáncer. Existen técnicas emergentes, como ASL, BOLD, RM elastografía, CEST e hiperpolarización, que aportan un nuevo tipo de información y que están cerca de su integración en la clínica diaria. Además, existe un gran interés en el estudio de la heterogeneidad tumoral con imagen como factor pronóstico y de resistencia al tratamiento. Para ello, se están aplicando nuevos métodos de análisis de los protocolos multiparamétricos, y a su vez se están desarrollando nuevos biomarcadores oncológicos integrando la información de la RM con los datos clínicos, analíticos, genéticos e histológicos, gracias a la aplicación del big data y la inteligencia artificial. En esta revisión se analizan varias técnicas emergentes de RM que permiten evaluar las características fisiológicas, metabólicas y mecánicas del cáncer, así como sus principales aplicaciones clínicas. Además, se resumen los métodos de análisis más novedosos de la información radiológica funcional en oncología


Current multiparameter MRI protocols integrate structural, physiological, and metabolic information about cancer. Emerging techniques such as arterial spin-labeling (ASL), blood oxygen level dependent (BOLD), MR elastography, chemical exchange saturation transfer (CEST), and hyperpolarization provide new information and will likely be integrated into daily clinical practice in the near future. Furthermore, there is great interest in the study of tumor heterogeneity as a prognostic factor and in relation to resistance to treatment, and this interest is leading to the application of new methods of analysis of multiparametric protocols. In parallel, new oncologic biomarkers that integrate the information from MR with clinical, laboratory, genetic, and histologic findings are being developed, thanks to the application of big data and artificial intelligence. This review analyzes different emerging MR techniques that are able to evaluate the physiological, metabolic, and mechanical characteristics of cancer, as well as the main clinical applications of these techniques. In addition, it summarizes the most novel methods of analysis of functional radiologic information in oncology


Assuntos
Humanos , Neoplasias/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Medicina de Precisão/métodos , Técnicas de Imagem por Elasticidade/métodos , Espectroscopia de Prótons por Ressonância Magnética/métodos , Hipóxia Tumoral , Radiogenética/tendências
6.
Radiología (Madr., Ed. impr.) ; 60(supl.1): 43-52, mayo 2018. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-175337

RESUMO

En la actualidad, tanto las imágenes como los datos que generan y los informes que se emiten son digitales y constituyen una fuente de datos fiable. Los informes pueden clasificarse, en función de su contenido, formato y tipo de datos, como organizado (texto libre en lenguaje natural), predefinido (con plantillas y guías construidas con campos previamente determinados con lenguaje natural tipo BI-RADS y PI-RADS) y estructurado (con desplegables en forma de preguntas, con diversas posibles respuestas, previamente pactadas en el equipo multidisciplinario, con léxicos estandarizados y estructurado como base de datos, con información trazable y explotable mediante herramientas estadísticas y de minería de datos). Este informe estructurado, compatible con MRRT (Management of Radiology Report Templates), permite incorporar información cuantitativa relacionada con el análisis digital de los datos de las imágenes adquiridas para describir, mediante radiómica (características y parámetros), las propiedades y el comportamiento de los tejidos con exactitud y veracidad. En conclusión, los datos digitales estructurados (imágenes, texto, mediciones, radiómica, biomarcadores de imagen) deben integrarse en un informe informatizado que permita su indexación en grandes repositorios. Estos bancos de datos radiológicos son fundamentales en la medicina personalizada para explotar la información sanitaria, fenotipificar las lesiones y enfermedades, y extraer conclusiones


Nowadays, the images and information generated in imaging tests, as well as the reports that are issued, are digital and represent a reliable source of data. Reports can be classified according to their content and to the type of information they include into three main types: organized (free text in natural language), predefined (with templates and guidelines elaborated with previously determined natural language like that used in BI-RADS and PI-RADS), or structured (with drop-down menus displaying questions with various possible answers that have been agreed on with the rest of the multidisciplinary team, which use standardized lexicons and are structured in the form of a database with data that can be traced and exploited with statistical tools and data mining). The structured report, compatible with Management of Radiology Report Templates (MRRT), makes it possible to incorporate quantitative information related with the digital analysis of the data from the acquired images to accurately and precisely describe the properties and behavior of tissues by means of radiomics (characteristics and parameters). In conclusion, structured digital information (images, text, measurements, radiomic features, and imaging biomarkers) should be integrated into computerized reports so that they can be indexed in large repositories. Radiologic databanks are fundamental for exploiting health information, phenotyping lesions and diseases, and extracting conclusions in personalized medicine


Assuntos
Humanos , Registros Médicos/normas , Neoplasias/diagnóstico por imagem , Comunicação em Saúde/métodos , Radiografia/normas , Sistemas de Informação em Radiologia/organização & administração , Medicina de Precisão/tendências , Biomarcadores/análise , Biomarcadores Tumorais/análise , Radiogenética/tendências
7.
Philos Ethics Humanit Med ; 12(1): 8, 2017 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-29082852

RESUMO

This paper describes an episode in the life of the prominent plant radiation geneticist, Lewis J. Stadler (1897-1954) during which he became a target of the Federal Bureau of Investigation (FBI) concerning loyalty to the United States due to possible associations with the communist party. The research is based on considerable private correspondence of Dr. Stadler, the FBI interrogatory questions and Dr. Stadler's answers and letters of support for Dr. Stadler by leading scientists such as, Hermann J. Muller.


Assuntos
Política , Radiogenética , História do Século XX , Humanos , Radiogenética/história , Estados Unidos
8.
Yakugaku Zasshi ; 135(11): 1197-211, 2015.
Artigo em Japonês | MEDLINE | ID: mdl-26521869

RESUMO

The linear no-threshold model (LNT) was recommended in 1956, with abandonment of the traditional threshold dose-response for genetic risk assessment. Adoption of LNT by the International Commission on Radiological Protection (ICRP) became the standard for radiation regulation worldwide. The ICRP recommends a dose limit of 1 mSv/year for the public, which is too low and which terrorizes innocent people. Indeed, LNT arose mainly from the lifespan survivor study (LSS) of atomic bomb survivors. The LSS, which asserts linear dose-response and no threshold, is challenged mainly on three points. 1) Radiation doses were underestimated by half because of disregard for major residual radiation, resulting in cancer risk overestimation. 2) The dose and dose-rate effectiveness factor (DDREF) of 2 is used, but the actual DDREF is estimated as 16, resulting in cancer risk overestimation by several times. 3) Adaptive response (hormesis) is observed in leukemia and solid cancer cases, consistently contradicting the linearity of LNT. Drastic reduction of cancer risk moves the dose-response curve close to the control line, allowing the setting of a threshold. Living organisms have been evolving for 3.8 billion years under radiation exposure, naturally acquiring various defense mechanisms such as DNA repair mechanisms, apoptosis, and immune response. The failure of LNT lies in the neglect of carcinogenesis and these biological mechanisms. Obstinate application of LNT continues to cause tremendous human, social, and economic losses. The 60-year-old LNT must be rejected to establish a new scientific knowledge-based system.


Assuntos
Modelos Lineares , Medição de Risco , Animais , Exposição Ambiental , Acidente Nuclear de Fukushima , Humanos , Neoplasias Induzidas por Radiação , Armas Nucleares , Radiogenética , Proteção Radiológica , Radiometria
9.
J Hist Biol ; 48(1): 67-98, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25001362

RESUMO

This article traces disagreements about the genetic effects of low-dose radiation exposure as waged by James Neel (1915-2000), a central figure in radiation studies of Japanese populations after World War II, and Yuri Dubrova (1955-), who analyzed the 1986 Chernobyl nuclear power plant accident. In a 1996 article in Nature, Dubrova reported a statistically significant increase in the minisatellite (junk) DNA mutation rate in the children of parents who received a high dose of radiation from the Chernobyl accident, contradicting studies that found no significant inherited genetic effects among offspring of Japanese A-bomb survivors. Neel's subsequent defense of his large-scale longitudinal studies of the genetic effects of ionizing radiation consolidated current scientific understandings of low-dose ionizing radiation. The article seeks to explain how the Hiroshima/Nagasaki data remain hegemonic in radiation studies, contextualizing the debate with attention to the perceived inferiority of Soviet genetic science during the Cold War.


Assuntos
Acidente Nuclear de Chernobyl , DNA Satélite/efeitos da radiação , Radiogenética/história , Relação Dose-Resposta à Radiação , História do Século XX , Humanos , Japão , Repetições Minissatélites/efeitos da radiação , Mutação/efeitos da radiação , U.R.S.S. , Ucrânia , Estados Unidos , II Guerra Mundial
10.
Bioelectromagnetics ; 35(7): 497-511, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25196377

RESUMO

The present experimental study was carried out with rats to evaluate the effects of whole body exposure to 2.14 GHz band code division multiple access (W-CDMA) signals for 20 h a day, over three generations. The average specific absorption rate (SAR, in unit of W/kg) for dams was designed at three levels: high (<0.24 W/kg), low (<0.08 W/kg), and 0 (sham exposure). Pregnant mothers (4 rats/group) were exposed from gestational day (GD) 7 to weaning and then their offspring (F1 generation, 4 males and 4 females/dam, respectively) were continuously exposed until 6 weeks of age. The F1 females were mated with F1 males at 11 weeks old, and then starting from GD 7, they were exposed continuously to the electromagnetic field (EMF; one half of the F1 offspring was used for mating, that is, two of each sex per dam and 8 males and 8 females/group, except for all offspring for the functional development tests). This protocol was repeated in the same manner on pregnant F2 females and F3 pups; the latter were killed at 10 weeks of age. No abnormalities were observed in the mother rats (F0 , F1 , and F2 ) and in the offspring (F1 , F2 , and F3 ) in any biological parameters, including neurobehavioral function. Thus, it was concluded that under the experimental conditions applied, multigenerational whole body exposure to 2.14 GHz W-CDMA signals for 20 h/day did not cause any adverse effects on the F1 , F2 , and F3 offspring.


Assuntos
Encéfalo/efeitos da radiação , Telefone Celular , Campos Eletromagnéticos , Animais , Peso Corporal/efeitos da radiação , Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Comportamento Exploratório/efeitos da radiação , Feminino , Masculino , Exposição Materna , Aprendizagem em Labirinto/efeitos da radiação , Atividade Motora/efeitos da radiação , Tamanho do Órgão , Exposição Paterna , Radiogenética , Radiometria , Ratos Sprague-Dawley , Reprodução/efeitos da radiação
11.
Conn Med ; 78(3): 178-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24772839
13.
Estud. av ; 27(77): 34-35, jan.-abr. 2013. ilus
Artigo em Português | LILACS | ID: lil-696219

RESUMO

Entrevista feita por jornalistas irlandeses, por ocasião da conferência de imprensa de Ady Roche (Chernobyl Children's Project (http://www.chernobylinternational.com), Minsk, abril de 2000.Tradução de Paulo Neves e revisão de Emico Okuno e Joaquim Francisco de Carvalho. O original em francês encontra-se à disposição do leitor para eventual consulta.


Assuntos
Masculino , Feminino , Criança , Humanos , Radiação , Efeitos da Radiação , Exposição à Radiação , Radiogenética , Lesões por Radiação , Radiação Ionizante , Crianças com Deficiência , Entrevistas como Assunto
14.
Mutat Res ; 752(1): 1-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22948037

RESUMO

H. J. Muller is best known for his Nobel Prize work on the induction of mutations by ionizing radiation. Geneticists are less familiar with his contributions to mutation and how he related the process of mutagenesis to the gene and distinguished gene mutations from other genetic and epigenetic events such as polyploidy, chromosome rearrangements, and position effects. The hallmark of Muller's contributions is his design of genetic stocks to solve genetic problems and allow experimentation to reveal new phenomena. In this review I relate Muller's personality to his teaching and research and present a history of Muller's ideas on mutation from his first days in Morgan's fly lab to his final thoughts on what became called "Muller's ratchet", a term he did not get to enjoy because it was coined seven years after his death.


Assuntos
Genética/história , Mutação , Evolução Biológica , História do Século XIX , História do Século XX , Radiogenética/história , Pesquisa , Estados Unidos
15.
Genetics ; 193(1): 229-41, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23105010

RESUMO

Adaptive dynamics formalism demonstrates that, in a constant environment, a continuous trait may first converge to a singular point followed by spontaneous transition from a unimodal trait distribution into a bimodal one, which is called "evolutionary branching." Most previous analyses of evolutionary branching have been conducted in an infinitely large population. Here, we study the effect of stochasticity caused by the finiteness of the population size on evolutionary branching. By analyzing the dynamics of trait variance, we obtain the condition for evolutionary branching as the one under which trait variance explodes. Genetic drift reduces the trait variance and causes stochastic fluctuation. In a very small population, evolutionary branching does not occur. In larger populations, evolutionary branching may occur, but it occurs in two different manners: in deterministic branching, branching occurs quickly when the population reaches the singular point, while in stochastic branching, the population stays at singularity for a period before branching out. The conditions for these cases and the mean branching-out times are calculated in terms of population size, mutational effects, and selection intensity and are confirmed by direct computer simulations of the individual-based model.


Assuntos
Evolução Molecular , Modelos Genéticos , Radiogenética , Algoritmos , Simulação por Computador , Deriva Genética , Característica Quantitativa Herdável , Seleção Genética
17.
Vestn Ross Akad Med Nauk ; (9): 63-8, 2011.
Artigo em Russo | MEDLINE | ID: mdl-22145375

RESUMO

The authors summarize results of 25-year selective cytogenetic monitoring of the priority groups in different periods after the Chernobyl accident. The increase in intensity of somatic chromosome mutagenesis in exposed individuals as a result of both targeted and non-targeted radiation-induced cytogenetic effects has been confirmed including delayed, transmissible, hidden chromosome instability and the bystander effect.


Assuntos
Efeito Espectador/genética , Acidente Nuclear de Chernobyl , Instabilidade Cromossômica , Linfócitos/efeitos da radiação , Mutagênese , Lesões por Radiação/genética , Análise Citogenética , Humanos , Linfócitos/metabolismo , Monitorização Fisiológica/métodos , Reatores Nucleares , Órgãos em Risco/efeitos da radiação , Radiogenética/métodos , Radiação Ionizante , Fatores de Risco , Tempo
18.
Mutat Res ; 718(1-2): 18-23, 2011 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-21075215

RESUMO

Although no statistically significant hereditary effects have yet been detected in the children of survivors from the atomic bombings in Hiroshima and Nagasaki, recent animal studies have found that exposure to ionizing radiation can cause genomic and epigenomic instability in the exposed individuals, as well as their offspring, and therefore, may have much larger genetic effects than predicted by earlier studies. When individuals are exposed to various environmental insults, including radiation, individual sensitivity to the insults often varies. Variance in germ-line response to radiation among individuals has been widely recognized, but it is difficult to address due to the use of inbred strains and the limited number of offspring that can be produced by a pair of mice, the common model used to study genetic effects of radiation. Herein is the first study to examine individual family responses to ionizing radiation using a parent-pedigree approach in an outbred strain of a vertebrate model, the Japanese medaka fish. Changes in frequencies of radiation-induced germline mutations at nine microsatellite loci were examined in the same families before and after exposure to one of four acute doses of ionizing radiation (0.1, 0.5, 2.5, 5Gy, plus sham-exposed controls). Families varied significantly in pre-exposure mutation frequencies and responses to irradiation, but germline mutations were elevated in at least one family after 0.1, 0.5, and 5Gy exposures. Variance among individuals in sensitivity to radiation is well documented for many endpoints, and our work now extends these endpoints to include germ-line mutations. Further studies are needed to elucidate dose response, effects at varying stages of spermatogenesis, and the mechanisms underlying the variance in these individual responses to radiation.


Assuntos
Epigênese Genética/efeitos da radiação , Instabilidade Genômica/efeitos da radiação , Mutação em Linhagem Germinativa , Oryzias/genética , Animais , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Camundongos , Repetições de Microssatélites/efeitos da radiação , Modelos Animais , Modelos Genéticos , Linhagem , Radiogenética
19.
Mutat Res ; 718(1-2): 1-9, 2011 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-21078408

RESUMO

The traditionally accepted biological basis for the late stochastic effects of ionizing radiation (cancer and hereditary disease), i.e. target theory, has so far been unable to accommodate the more recent findings of non-cancer disease and the so-called non-targeted effects, genomic instability and bystander effect, thus creating uncertainty in radiation risk estimation. We propose that ionizing radiation can give rise to these effects through two distinct and independent routes, one essentially genetic, termed here type A, and the other essentially epigenetic, termed type B. Type B processes entail envisaging phenotype as represented by a dynamic attractor and radiation acting as an agent that stresses cellular processes leading to the adoption of a variant attractor/phenotype. Evidence from the literature indicates that type B processes can lead to the inheritance of variant cell attractors and mediate a category of trans-generational effects quite distinct from classical Mendelian inherited disease, which is type A. The causal relationships for radiation-induced somatic human health detriment, i.e., cancer and non-cancer (e.g., cardiovascular) disease, are discussed from the point of view of the proposed classification. This approach unifies at a fundamental level the heritable and late somatic effects of radiation into a single causal framework that has the potential to be extended to the effects of the other environmental agents damaging to health.


Assuntos
Modelos Biológicos , Efeitos da Radiação , Animais , Efeito Espectador/efeitos da radiação , Epigênese Genética/efeitos da radiação , Doenças Genéticas Inatas/etiologia , Instabilidade Genômica/efeitos da radiação , Células Germinativas/efeitos da radiação , Humanos , Modelos Genéticos , Mutação , Neoplasias Induzidas por Radiação/genética , Radiogenética , Medição de Risco , Processos Estocásticos
20.
Mutat Res ; 701(1): 27-37, 2010 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-20398788

RESUMO

Experiments were carried out to explore the correlation between chromatin conformation changes in the presence of DNA lesions and the formation of radiation-induced chromosomal aberrations. To modulate the onset and dynamics of chromatin conformation changes following irradiation, premature chromosome condensation (PCC) was induced by means of cell fusion. G2-check point abrogation by caffeine or elevated heat treatment was also applied. In addition, transfer of irradiated mitotic cells was employed either into depleted media to restrain them from proceeding through G1/S, or holding them further in colcemid to avoid M/G1 transition. To investigate the correlation between efficiency of chromosomal conformation changes and chromosomal breakage in irradiated G0 peripheral blood lymphocytes, cell fusion with different mitotic PCC-inducer cells was used. The experimental evidence supports the hypothesis that functional cell-cycle chromatin conformation changes in the presence of DNA damage are important determinants in the formation of radiation-induced chromosomal aberrations. Specifically, it is proposed here that following irradiation, chromatin structure may not be broken but instead it unfolds to a conformation that is more accessible to repair enzymes at the sites of DNA lesions. If subsequent chromosomal conformation changes occur while DNA is still being repaired, such changes will lead into an energetically unfavorable state, thus exerting mechanical stress on the unfolded chromatin at the damaged sites, which will in turn result into chromatid breaks that may not be able to restitute or mis-rejoin. Therefore, this biophysical conversion process of DNA damage into chromatid breaks as such is antagonistic to the DNA repair process. Alternatively, in the absence of chromosomal conformation changes, either DNA repair will take place efficiently or DNA misrepair will cause the formation of exchanges and chromosomal rearrangements. Consequently, the type and yield of radiation-induced chromosomal aberrations at a given cell cycle stage will be the combined effect of the interaction, at that particular stage, of the DNA repair process and the proposed conversion process of DNA lesions into chromatid breaks.


Assuntos
Cromatina/química , Aberrações Cromossômicas , Dano ao DNA , Radiação Ionizante , Animais , Células CHO , Cricetinae , Cricetulus , Quebras de DNA de Cadeia Dupla , Humanos , Interfase , Modelos Genéticos , Conformação Molecular , Fosforilação , Radiogenética
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