RESUMO
The identification of substances that prevent or minimize the detrimental effects of ionizing radiation is an essential undertaking. The aim of this paper was to evaluate and compare the radioprotective potential of chlorophyllin, protoporphyrin and bilirubin, with amifostine®, an US Food & Drug Administration approved radioprotector Using the somatic mutation and recombination assay in the Drosophila melanogaster wing, it was found that pretreatment (1-9â¯h) with any of the porphyrins or amifostine® alone, did not affect the larva-adult viability or the basal frequency of mutation. However, they were associated with significant reductions in frequency of somatic mutation and recombination compared with the gamma-irradiated (20â¯Gy) control as follows: bilirubin (69.3 %)> chlorophyllin (40.0 %)> protoporphyrin (39.0 %)> amifostine® (19.7 %). Bilirubin also caused a 16 % increase in larva-adult viability with 3â¯h of pretreatment respect to percentage induced in 20â¯Gy control group. Whilst amifostine® was associated with lower genetic damage after pre-treatment of 1 and 3â¯h, this did not attain significance. These findings suggest that the tested porphyrins may have some potential as radioprotectant agents.
Assuntos
Amifostina/farmacologia , Bilirrubina/farmacologia , Clorofilídeos/farmacologia , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/efeitos da radiação , Protoporfirinas/farmacologia , Protetores contra Radiação/farmacologia , Animais , Drosophila melanogaster/genética , Feminino , Masculino , Testes de Mutagenicidade , Mutação/efeitos dos fármacos , Recombinação Genética/efeitos dos fármacos , Asas de Animais/efeitos dos fármacos , Asas de Animais/efeitos da radiaçãoRESUMO
Many studies have revealed that ascorbic acid (Aa) acts as a powerful inhibitor of genetic damage. The objetive of the present study was to evaluate the radioprotector effect of Aa at two diferent radiation dose rates. The somatic mutation and recombination test in Drosophila melanogaster was used. 48 h larvae were treated for 24 h with 25, 50 and 100 mM of Aa. After pretreatment, larvae were irradiated with 20 Gy of gamma rays administered at 36 or 960 Gy/h. Toxicity, development rate and frequency of mutant spots were recorded. Results provide evidence of a radioprotective effect for all tested concentrations of Aa only when 20 Gy were delivered at 36 Gy/h and only with 25 mM using the 960 Gy/h. To consider the use of Aa as radioprotector or therapeutic agent, it is necessary to know its potential under different situations to avoid unwanted injuries.
Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Drosophila melanogaster/efeitos dos fármacos , Raios gama/efeitos adversos , Protetores contra Radiação/farmacologia , Animais , Dano ao DNA , Relação Dose-Resposta à Radiação , Drosophila melanogaster/genética , Drosophila melanogaster/efeitos da radiação , Feminino , Larva/efeitos dos fármacos , Larva/genética , Larva/efeitos da radiação , Masculino , Mutação , Asas de Animais/anormalidades , Asas de Animais/efeitos dos fármacos , Asas de Animais/efeitos da radiaçãoRESUMO
Ionizing radiation plays a key role in the adaptation of an individual organism to environmental pollution, at the same time, it has biological effects that depend on radiation intensity or dose rate (DR). Although the effect of DR has been studied in vitro, the phenomenon known as the inverse effect of DR, which indicates as it decreases that the induction of damage is greater, has not been widely studied in vivo. The present study is aimed to test 0.5 and 1 Gy in somatic cells of the wing of D. melanogaster, administered at 5.4 or 34.3 Gy/h and from 0.037 to 0.3 mM of CrO3 as conditioning treatment. No changes were found in larva-to-adult viability. A protective as well as a cross effect of pre-exposure to different DR and CrO3 concentrations against genetic damage induced by 20 Gy or 1 mM CrO3 was evident.
Assuntos
Compostos de Cromo/farmacologia , Drosophila melanogaster/genética , Asas de Animais/citologia , Animais , Meios de Cultivo Condicionados , Dano ao DNA/efeitos dos fármacos , Relação Dose-Resposta à Radiação , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/efeitos da radiação , Feminino , Tolerância a Radiação , Radiação Ionizante , Asas de Animais/efeitos dos fármacos , Asas de Animais/efeitos da radiaçãoRESUMO
Natural radiation of geological origin is a common phenomenon in Brazil, a country where radioactive agents such as uranium may be often found. As an unstable atom, uranium undergoes radioactive decay with the generation of a series of decay by-products, including radon, which may be highly genotoxic and trigger several pathological processes, among which cancer. Because it is a gas, radon may move freely between cracks and gaps in the ground, seeping upwards into the buildings and in the environment. In this study, two Drosophila melanogaster Meigen (Diptera, Drosophilidae) strains called Oregon-R and Wild (collected in a non-radioactive environment) were exposed to atmospheric radiation in the Lajes Pintadas city, in the semiarid zone of northeastern Brazil. After six days of environmental exposure, the organisms presented genetic damage significantly higher than that of the negative control group. The genotoxic effects observed reinforce the findings of other studies carried out in the same region, which warn about the environmental risks related to natural radioactivity occurrence. The results also validate the use of the Comet assay in hemocytes of D. melanogaster as a sensitive test to detect genotoxicity caused by natural radiation, and the use of a recently collected D. melanogaster strain in the environmental of radon.
Assuntos
Radiação de Fundo/efeitos adversos , Ensaio Cometa/métodos , Dano ao DNA , Drosophila melanogaster/efeitos da radiação , Exposição Ambiental , Radônio/toxicidade , Animais , Brasil , Clima Desértico , Drosophila melanogaster/genética , Hemócitos/química , Sensibilidade e Especificidade , Urânio/toxicidadeRESUMO
PURPOSE: The aim of this study was to investigate tolerance to UV-C (ultraviolet C, 280-100 nm) radiation in Drosophila melanogaster, implementing a quantitative trait locus (QTL) mapping approach. This is of interest to test for genetic variation in survival to UV (ultraviolet) radiation. MATERIALS AND METHODS: We performed a QTL scan in D. melanogaster recombinant inbred lines (RIL) constructed from parental stocks derived from a crossing between northern and southern hemisphere populations that segregated substantial genetic variation in thermal resistance in a previous study. Here, two experimental treatments were implemented: Continuous and cyclic UV-C radiation. RESULTS: Significant QTL were detected on all three major chromosomes. Among these, multiple trait composite interval mapping revealed a significant QTL in the pericentromeric region of chromosome 2, a genome region consistently implicated in thermotolerance in previous studies. CONCLUSIONS: This study shows substantial genetic variation for UV-C radiation resistance in D. melanogaster, with QTL for survival to UV-C radiation generally overlapping with major thermotolerance QTL. The genetic architecture of UV-C radiation resistance appears to be more complex in continuously irradiated individuals.
Assuntos
Drosophila melanogaster/genética , Drosophila melanogaster/efeitos da radiação , Locos de Características Quantitativas/genética , Locos de Características Quantitativas/efeitos da radiação , Tolerância a Radiação/genética , Tolerância a Radiação/efeitos da radiação , Taxa de Sobrevida , Animais , Relação Dose-Resposta à Radiação , Doses de Radiação , Raios UltravioletaRESUMO
Circadian rhythms allow organisms to time biological processes to the most appropriate phases of the day-night cycle. Post-transcriptional regulation is emerging as an important component of circadian networks, but the molecular mechanisms linking the circadian clock to the control of RNA processing are largely unknown. Here we show that PROTEIN ARGININE METHYL TRANSFERASE 5 (PRMT5), which transfers methyl groups to arginine residues present in histones and Sm spliceosomal proteins, links the circadian clock to the control of alternative splicing in plants. Mutations in PRMT5 impair several circadian rhythms in Arabidopsis thaliana and this phenotype is caused, at least in part, by a strong alteration in alternative splicing of the core-clock gene PSEUDO RESPONSE REGULATOR 9 (PRR9). Furthermore, genome-wide studies show that PRMT5 contributes to the regulation of many pre-messenger-RNA splicing events, probably by modulating 5'-splice-site recognition. PRMT5 expression shows daily and circadian oscillations, and this contributes to the mediation of the circadian regulation of expression and alternative splicing of a subset of genes. Circadian rhythms in locomotor activity are also disrupted in dart5-1, a mutant affected in the Drosophila melanogaster PRMT5 homologue, and this is associated with alterations in splicing of the core-clock gene period and several clock-associated genes. Our results demonstrate a key role for PRMT5 in the regulation of alternative splicing and indicate that the interplay between the circadian clock and the regulation of alternative splicing by PRMT5 constitutes a common mechanism that helps organisms to synchronize physiological processes with daily changes in environmental conditions.
Assuntos
Processamento Alternativo/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/fisiologia , Proteínas Metiltransferases/metabolismo , Proteína-Arginina N-Metiltransferases/metabolismo , Animais , Arabidopsis/enzimologia , Arabidopsis/genética , Arabidopsis/efeitos da radiação , Proteínas de Arabidopsis/genética , Sequência de Bases , Relógios Circadianos/genética , Ritmo Circadiano/genética , Escuridão , Proteínas de Drosophila/genética , Drosophila melanogaster/enzimologia , Drosophila melanogaster/genética , Drosophila melanogaster/efeitos da radiação , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Luz , Metilação , Mutação , Proteínas Circadianas Period/genética , Fenótipo , Proteínas Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/genética , Precursores de RNA/genética , Precursores de RNA/metabolismo , Sítios de Splice de RNA/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Spliceossomos/metabolismo , Fatores de Transcrição/genéticaRESUMO
It has been demonstrated that the human tumor suppressor p53 has an important role in modulating histone modifications after UV light irradiation. In this work we explored if the p53 Drosophila homologue has a similar role. Taking advantage of the existence of polytene chromosomes in the salivary glands of third instar larvae, we analyzed K9 and K14 H3 acetylation patterns in situ after UV irradiation of wild-type and Dmp53 null flies. As in human cells, after UV damage there is an increase in H3 acetylation in wild-type organisms. In Dmp53 mutant flies, this response is significantly affected at the K9 position. These results are similar to those found in human p53 mutant tumor cells with one interesting difference, only the basal H3 acetylation of K14 is reduced in Dmp53 mutant flies, while the basal H3-K9 acetylation is not affected. This work shows, that the presence of Dmp53 is necessary to maintain normal H3-K14 acetylation levels in Drosophila chromatin and that the function of p53 to maintaining histone modifications, is conserved in Drosophila and humans.
Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Histonas/metabolismo , Larva/efeitos da radiação , Proteína Supressora de Tumor p53/metabolismo , Acetilação , Animais , Cromossomos/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/efeitos da radiação , Humanos , Larva/metabolismo , Proteína Supressora de Tumor p53/genética , Raios UltravioletaRESUMO
The generation of electricity in nuclear power plants produces an increase in background radiation that could possibly have some impact on the organisms that live in that area. In order to identify and quantify any such possible effect, the natural populations of two sibling species, D. melanogaster and D. simulans, that live in the immediate vicinity of the first Mexican Nuclear Power Plant were analyzed for a period of 10 years. Collections of flies were made at two sites, one close to and one farther from the power plant, during the pre and operational stages of the reactor, and their egg-to-adult viability was analyzed. The data obtained indicate that in both sites, the egg-to-adult viability was generally higher in D. melanogaster than in D. simulans. Further, a relationship was found between egg-to-adult viability and the season of the year (warm-wet or cool-dry season). Some differences were found between the two sites. It may be concluded that there is no negative impact on the Drosophila populations studied.
Assuntos
Contaminação Radioativa do Ar/efeitos adversos , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/efeitos da radiação , Centrais Elétricas , Animais , Monitoramento Ambiental/métodos , Crescimento DemográficoRESUMO
TFIIH is a multiprotein complex that has a central role in the RNA pol II mediated transcription, in DNA repair and in the control of the cell cycle. Mutations in some components of TFIIH are associated with three hereditary human syndromes: xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD). The p62 protein is a structural component of the TFIIH core and no syndromes have been identified up to date by mutations in this human gene. In this work we report the molecular and genetic characterization of the Drosophila melanogaster p62 gene (Dmp62). The Dmp62 gene product shows high identity with its human and mouse homologues. Using computer analysis we identified several common motifs in the p62 proteins from different organisms, suggesting that these motifs could be involved in possible protein-protein interactions within the TFIIH complex or with other transcription and DNA repair factors. The Dmp62 transcript is expressed at similar levels throughout development, although there is a significant increase of the transcript level during the late embryogenesis and in the adult male. The analysis of a Drosophila line with a P-element enhancer trap insertion at the Dmp62 5'-UTR that directs the lac-Z expression from the Dmp62 promoter, showed a high level of expression in the gut, the testis and the pericardial cells. A P-element that disrupts the Dmp62 gene (Dmp62mut) produces early embryo lethality in homozygous flies. Heterozygous Dmp62mut larvae are more sensitive to UV light irradiation, and those individuals that are able to develop into adults have severe abdominal cuticular damage after UV light irradiation.
Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/efeitos da radiação , Regulação da Expressão Gênica no Desenvolvimento , Fatores Associados à Proteína de Ligação a TATA , Fator de Transcrição TFIID , Fatores de Transcrição TFII/genética , Sequência de Aminoácidos , Animais , Clonagem Molecular , Primers do DNA/química , Reparo do DNA/genética , Proteínas de Drosophila/biossíntese , Drosophila melanogaster/genética , Embrião não Mamífero/metabolismo , Elementos Facilitadores Genéticos , Humanos , Óperon Lac , Camundongos , Dados de Sequência Molecular , Mutação , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas , RNA Mensageiro/metabolismo , Homologia de Sequência de Aminoácidos , Distribuição Tecidual , Fator de Transcrição TFIIH , Fatores de Transcrição TFII/biossíntese , Raios Ultravioleta , beta-Galactosidase/metabolismoRESUMO
A method to obtain the absorbed dose in Drosophila melanogaster irradiated in the thermal column facility of the Triga Mark III Reactor has been developed. The method is based on the measurements of neutron activation of gold foils produced by neutron capture to obtain the neutron fluxes. These fluxes, combined with the calculations of kinetic energy released per unit mass, enables one to obtain the absorbed doses in Drosophila melanogaster.