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BACKGROUND: Ventricular septal defect (VSD) is the most common subtype of congenital heart disease. In the present study, we aimed to determine whether chromosome aberration was associated with the occurrence of VSD and evaluate the association of VSD size, location and chromosome aberration with adverse outcomes in the Chinese fetuses. METHODS: Fetuses with VSD and comprehensive follow-up data were included and evaluated retrospectively. Medical records were used to collect epidemiological data and foetal outcomes. For VSD fetuses, conventional karyotype and microarray analysis were conducted. After adjusting confounding factors by using multivariable logistic regression analyses, the association between chromosome variations and VSD occurrence was explored. The association between defect size, location and chromosome aberrations and adverse foetal outcomes was also investigated. RESULTS: Chromosome aberration was the risk factor for VSD occurrence, raising 6.5-fold chance of developing VSD. Chromosome aberration, peri-membranous site and large defect size of VSD were significant risk factors of adverse fetal outcome. Chromosome aberrations, including pathogenic copy number variations (CNVs) and variations of uncertain significance (VUS), were both risk factors, increasing the risk of the adverse fetal outcome by 55.9 times and 6.7 times, respectively. The peri-membranous site would increase 5.3-fold risk and defects larger than 5 mm would increase the 7.1-fold risk for poor fetal outcome. CONCLUSIONS: The current investigation revealed that chromosomal abnormalities, large defects, and the peri-membranous site were all risk factors for poor fetal outcomes. Our study also indicated that chromosome aberration was one of risk factors for the VSD occurrence.
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Variações do Número de Cópias de DNA , Comunicação Interventricular , Humanos , Estudos Retrospectivos , Fatores de Risco , Feto , Comunicação Interventricular/epidemiologia , Comunicação Interventricular/genética , Prognóstico , Aberrações Cromossômicas , Análise FatorialRESUMO
There has been some controversy over the use of radiobiological models when modeling the dose-response curves of ionizing radiation (IR)-induced chromosome aberration and tumor prevalence, as those curves usually show obvious non-targeted effects (NTEs) at low doses of high linear energy transfer (LET) radiation. The lack of understanding the contribution of NTEs to IR-induced carcinogenesis can lead to distinct deviations of relative biological effectiveness (RBE) estimations of carcinogenic potential, which are widely used in radiation risk assessment and radiation protection. In this work, based on the initial pattern of two classes of IR-induced DNA double-strand breaks (DSBs) clustering in chromatin domains and the subsequent incorrect repair processes, we proposed a novel radiobiological model to describe the dose-response curves of two carcinogenic-related endpoints within the same theoretical framework. The representative experimental data was used to verify the consistency and validity of the present model. The fitting results indicated that, compared with targeted effect (TE) and NTE models, the current model has better fitting ability when dealing with the experimental data of chromosome aberration and tumor prevalence induced by multiple types of IR with different LETs. Notably, the present model without introducing an NTE term was adequate to describe the dose-response curves of IR-induced chromosome aberration and tumor prevalence with NTEs in low-dose regions. Based on the fitting parameters, the LET-dependent RBE values were calculated for three given low doses. Our results showed that the RBE values predicted by the current model gradually decrease with the increase of doses for the endpoints of chromosome aberration and tumor prevalence. In addition, the calculated RBE was also compared with those evaluated from other models. These analyses show that the proposed model can be used as an alternative tool to well describe dose-response curves of multiple carcinogenic-related endpoints and effectively estimate RBE in low-dose regions.
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Quebras de DNA de Cadeia Dupla , Neoplasias , Humanos , Cromatina , Prevalência , Transferência Linear de Energia , Radiação Ionizante , Aberrações Cromossômicas , DNA/efeitos da radiação , Análise por Conglomerados , Relação Dose-Resposta à RadiaçãoRESUMO
Pyriproxyfen (PPX) is a pesticide/larvicide used to increase productivity in agriculture against insects by inhibiting development of insects' larvae. In this study, cytotoxic, genotoxic, and mutagenic effects of PPX were investigated in human peripheral lymphocytes and Salmonella typhimurium strains by performing chromosomal aberration, micronucleus (MN) tests, and Ames test, respectively. For the chromosome aberration (CA) and MN methods, blood from four healthy donors (two men and two women, nonsmokers) were used. Two hundred microliters of blood was inoculated into PbMax medium and prepared according to International Guidelines. For the Ames test, S. typhimurium TA98 and TA100 strains were used to detect frameshift and base pair substitution mutagens, respectively. PPX induced both the CA percentage and MN frequency in human peripheral lymphocytes and exhibited cytotoxic effects. In addition, it showed a mutagenic effect at all doses in TA98 and TA100 strains in the presence of S9mix; however, no such effect was observed in the absence of S9mix. According to the obtained results, it can be said that PPX has genotoxic and mutagenic potentials.
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Mutagênicos , Salmonella typhimurium , Masculino , Humanos , Feminino , Mutagênicos/toxicidade , Salmonella typhimurium/genética , Testes de Mutagenicidade/métodos , Aberrações Cromossômicas , Dano ao DNA , LinfócitosRESUMO
Previous research reported that prolonged benzene exposure during in utero fetal development causes greater fetal abnormalities than in adult-stage exposure. This phenomenon increases the risk for disease development at the fetal stage, particularly carcinogenesis, which is mainly associated with hematological malignancies. Benzene has been reported to potentially act via multiple modes of action that target the hematopoietic stem cell (HSCs) niche, a complex microenvironment in which HSCs and multilineage hematopoietic stem and progenitor cells (HSPCs) reside. Oxidative stress, chromosomal aberration and epigenetic modification are among the known mechanisms mediating benzene-induced genetic and epigenetic modification in fetal stem cells leading to in utero carcinogenesis. Hence, it is crucial to monitor exposure to carcinogenic benzene via environmental, occupational or lifestyle factors among pregnant women. Benzene is a well-known cause of adult leukemia. However, proof of benzene involvement with childhood leukemia remains scarce despite previously reported research linking incidences of hematological disorders and maternal benzene exposure. Furthermore, accumulating evidence has shown that maternal benzene exposure is able to alter the developmental and functional properties of HSPCs, leading to hematological disorders in fetus and children. Since HSPCs are parental blood cells that regulate hematopoiesis during the fetal and adult stages, benzene exposure that targets HSPCs may induce damage to the population and trigger the development of hematological diseases. Therefore, the mechanism of in utero carcinogenicity by benzene in targeting fetal HSPCs is the primary focus of this review.
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Benzeno , Leucemia , Criança , Humanos , Feminino , Gravidez , Benzeno/toxicidade , Células-Tronco Hematopoéticas/patologia , Leucemia/induzido quimicamente , Leucemia/genética , Feto/patologia , Carcinogênese/patologia , Hematopoese , Microambiente TumoralRESUMO
Strawberry tree (Arbutus unedo L.) honey (STH) has been used since ancient times as a folk medicine remedy, especially in certain Mediterranean countries. This honey, rich in phenolic content, is well recognized for its antioxidant, anti-inflammatory, and antimicrobial activities, and is used for the treatment of skin lesions as well as gastrointestinal and respiratory disorders. This study investigated whether STH alleviates genome damage in human peripheral blood lymphocytes produced by the cytotoxic drug irinotecan. The phenolic profile of STH was previously estimated by ultra-high-performance liquid chromatography coupled to a linear ion trap-Orbitrap hybrid mass spectrometer. The effects of STH were evaluated at three concentrations (1×, 5×, and 10×), based on the daily consumption of the honey by an adult person. After 2 h of in vitro exposure, standard lymphocyte cultures for the analysis of chromosome aberrations and the cytokinesis-block micronucleus cytome assay were established. Our results demonstrate that STH offered remarkable geno- and cytoprotection when administered with irinotecan. These findings are relevant for drawing preliminary conclusions regarding the in vitro safety of the tested honey. However, further studies are needed with the application of more complex experimental models.
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Ericaceae , Mel , Humanos , Mel/análise , Irinotecano/farmacologia , Antioxidantes/farmacologia , Ericaceae/química , Fenóis/análise , Análise CitogenéticaRESUMO
Preimplantation genetic testing (PGT) is the earliest form of prenatal diagnosis that has become an established procedure for couples at risk of passing a severe genetic disease to their offspring. At UMC Ljubljana, we conducted a retrospective register-based study to present 15 years of PGT service within the public healthcare system in Slovenia. We collected the data of the PGT cycles from 2004 to 2019 and compared clinical outcomes for chromosomal and monogenic diseases using different embryo biopsy and testing approaches. In addition, we assessed the extent to which PGT has become the preferred option compared to classic prenatal diagnostics. We treated 211 couples, 110 with single gene disorder, 88 with structural chromosome rearrangement and 13 for numerical chromosome aberration. There were 375 PGT cycles with oocyte retrieval, while embryo transfer was possible in 263 cases resulting in 78 deliveries and 84 children. Altogether, the clinical pregnancy rate per embryo transfer was 31% in 2004-2016 (blastomere biopsy) and 43% in 2017-19 (blastocyst biopsy), respectively. We assessed that approximately a third of couples would opt for PGT, while the rest preferred natural conception with prenatal diagnosis. Our results show that providing a PGT service within the public healthcare system has become a considerable option in pregnancy planning for couples at risk of transmitting a severe genetic disease to their offspring. In Slovenia, approximately a third of couples would opt for PGT. Although the number of cycles is small, our clinical results are comparable to larger centres.
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Background: Dental radiology represents the best model for evaluating the effects of low-dose ionizing radiation. Therefore, this study evaluated the awareness on radiation hygiene among dental ancillary personnel through a questionnaire and their absorbed doses by physical and biologic dosimetry. Methods: The multicentric study included two groups. Group I (N = 30) consisted of dental staff involved in dental radiology. An equal number of personnel who were not related to radiology formed the control group. Knowledge (K), attitude (A), and practice (P) of participants were assessed using a KAP questionnaire. Radiation exposure was evaluated by physical dosimetry at 3 time periods: at the beginning of the study (T1), after 10 months (T2), and at the end after 20 months (T3). Similarly, biologic dosimetry was also carried out at 3 time points by dicentric chromosome aberration assay. The data were compared using percentage analysis, analysis of variance (one-way analysis of variance), and Student's t- test. Results: The KAP survey demonstrated enhanced understanding of radiation protection measures and its sound practice by the participants. Physical dosimetry showed a significant increase in absorbed dose at 3 time points: T1, T2, and T3. However, no chromosomal aberrations were observed in blood lymphocytes for any of the participants in the optimized 4-day biodosimetry protocol. Conclusion: Good radiation protection protocols-safe distance from the radiation source and wear of lead aprons and thyroid collars-ensured low absorbed doses. The 4-day protocol is an important step toward developing biodosimetry laboratories in the Armed Forces Medical Services for clinical and national radiation countermeasure strategies.
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Objective: To analyze the level of chromosome aberration in lymphocytes of medical radiation workers and its influencing factors. Methods: From July to September 2020, 252 medical workers in a tertiary hospital were selected as the study subjects and 107 preserviceworkers were selected as the control group. The Chromosomal aberrations of peripheral blood lymphocytes were measured using conventional cytogenetic analysis method, and the differences were analyzed. Results: The frequencies of dicentric puls centric ring, total chromosome-type aberrations, and abnormal detection rate in the radiation group were significantly higher than those in the control group (Z=2.59, 3.74, 9.99, P<0.05). There was significant difference in the frequencies of dicentric plus centric ring and total chromosome-type aberrations among different types of work (χ(2)=8.59, 8.17, 11.39, P<0.05), and the frequencies of dicentric plus centric ring were significantly higher in the interventional radiology group than those in diagnostic radiology (χ(2)=2.90, P<0.05), While the rates of acentric fragment and total chromosome-type aberrations were significantly higher in the nuclear medicine group than those in diagnostic radiology (χ(2)=2.81, 3.19, P<0.05). The difference in the abnormal detection rate of chromosome aberrations between different types of work was statistically significant (P<0.05), and the rate in the interventional radiology group was significantly higher than that in the diagnostic radiology group (χ(2)=7.66, P<0.05). There was no significant difference in chromosome aberration level and abnormal detection rate among different working ages (P>0.05). Poisson regression analysis indicated that the type of work is a risk factor for chromosomal aberration [IRR=2.31 (nuclear medicine group), 1.66 (Radiation therapy), and 1.78 (interventional group) ; P<0.05]. Conclusion: Ionizing radiation causes certain radiation damage to medical radiology workers, and the frequencies of chromosome aberration in the radiation workers of nuclear medicine and interventional radiology groups are relatively high, so radiation protection should be strengthened to ensure the health of relevant workers.
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Aberrações Cromossômicas , Radiologia , Humanos , Centros de Atenção Terciária , Grupos Controle , LinfócitosRESUMO
Caryophyllideans are intestinal parasites of freshwater fishes, occupying a basal position among the 'true' tapeworms. We performed detailed cytogenetic analyses of the well-known caryophyllidean species Caryophyllaeus laticeps. For comparison, we also examined for the first time the chromosomes of Paracaryophyllaeus gotoi, a specific parasite of loaches in China. Both species showed a diploid chromosome number of 2n = 20, n = 10m. Chromomycin A3 (CMA3)/diamidino-2-phenylindole (DAPI) staining performed for the first time in the class Cestoda revealed CMA3+/DAPI− bands in the pericentromeric regions of the short arms of chromosome pair no. 7 in the karyotype of C. laticeps. Fluorescence in situ hybridization with the 18S rDNA probe confirmed the presence of a single cluster of major rDNA near the centromere on a pair of small chromosomes in both species. These findings support the hypothesis that the ancestral state in the family Caryophyllaeidae is a single interstitial cluster of major rDNA genes and thus one nucleolar organizer region per haploid genome. Our results, which we presented together with literature data plotted on a phylogenetic tree, show stability of caryophyllidean karyotypes at the genus level, but showed differences between genera without a clear phylogenetic signal. The data allowed us to at least formulate a hypothesis about the ancestral haploid chromosome number of n = 10 for the family Caryophyllaeidae and possibly for the sister family Capingentidae. In addition, we compared two populations of C. laticeps from water bodies with different levels of polychlorinated biphenyl contamination, showing a slightly increased incidence of chromosomal abnormalities at the contaminated site.
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Cestoides , Cipriniformes , Parasitos , Animais , Cestoides/genética , Análise Citogenética , DNA Ribossômico/genética , Hibridização in Situ Fluorescente , Cariótipo , Parasitos/genética , FilogeniaRESUMO
Gadobutrol and gadoversetamide are gadolinium-based contrast agents (GBCAs) widely used during magnetic resonance imaging examination. In this study, the genotoxicity of two GBCAs, gadobutrol and gadoversetamide, was investigated by using different endpoints: chromosome aberration (CAs), sister chromatid exchange (SCEs), and micronucleus (MNi). Human peripheral lymphocytes (PBLs) were treated with five concentrations (7 000, 14 000, 28 000, 56 000, and 112 000 µg/mL) of both agents. While a few concentrations of gadobutrol significantly increased abnormal cell frequency and CA/Cell, nearly all the concentrations of gadoversetamide significantly elevated the same aberrations. Similarly, the effect of gadoversetamide on the formation of SCEs was higher than those of gadobutrol. Only one concentration of gadoversetamide significantly increased MN% but no gadobutrol. The comet assay was applied for the only gadobutrol which induced a significant increase in tail intensity at the highest concentration only. On the other hand, significantly decreased mitotic index (MI) was observed following both substances, again gadoversetamide was slightly higher than those of the gadobutrol. The results revealed that both the contrast agents are likely to induce genotoxic risk in PBLs. However, different concentrations and treatment periods should be examined in vitro and specifically in vivo with different test systems for the safer usage of these contrast agents.
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Meios de Contraste , Gadolínio , Humanos , Testes para Micronúcleos , Meios de Contraste/toxicidade , Gadolínio/farmacologia , Troca de Cromátide Irmã , Linfócitos , Dano ao DNA , Aberrações Cromossômicas/induzido quimicamente , Imageamento por Ressonância MagnéticaRESUMO
Ionizing radiation causes chromosome aberrations, which are possible biomarkers to assess space radiation cancer risks. Using the Monte Carlo codes Relativistic Ion Tracks (RITRACKS) and Radiation-Induced Tracks, Chromosome Aberrations, Repair and Damage (RITCARD), we investigated how geometrical properties of the cell nucleus, irradiated with ion beams of linear energy transfer (LET) ranging from 0.22 keV/µm to 195 keV/µm, influence the yield of simple and complex exchanges. We focused on the effect of (1) nuclear volume by considering spherical nuclei of varying radii; (2) nuclear shape by considering ellipsoidal nuclei of varying thicknesses; (3) beam orientation; and (4) chromosome intermingling by constraining or not constraining chromosomes in non-overlapping domains. In general, small nuclear volumes yield a higher number of complex exchanges, as compared to larger nuclear volumes, and a higher number of simple exchanges for LET < 40 keV/µm. Nuclear flattening reduces complex exchanges for high-LET beams when irradiated along the flattened axis. The beam orientation also affects yields for ellipsoidal nuclei. Reducing chromosome intermingling decreases both simple and complex exchanges. Our results suggest that the beam orientation, the geometry of the cell nucleus, and the organization of the chromosomes within are important parameters for the formation of aberrations that must be considered to model and translate in vitro results to in vivo risks.
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Aberrações Cromossômicas , Cromossomos , Núcleo Celular/genética , Núcleo Celular/efeitos da radiação , Cromossomos/genética , Humanos , Transferência Linear de Energia , Método de Monte CarloRESUMO
INTRODUCTION: In Denmark, non-invasive prenatal testing (NIPT) has been used since 2013. We aimed to evaluate the early clinical use of NIPT in Danish public and private healthcare settings before NIPT became an integrated part of the national guidelines on prenatal screening and diagnosis in 2017. MATERIAL AND METHODS: NIPT data were collected between March 2013 and June 2017 from national public registries and private providers. Results from follow-up samples (chorionic villi, amniotic fluid, postnatal blood or fetal tissue) were included from The Danish Cytogenetics Central Registry and indications and outcome from The Danish Fetal Medicine Database. RESULTS: A total of 3936 NIPT results were included in the study from public hospitals (n = 3463, 88.0%) and private clinics (n = 473, 12.0%). The total number of prenatal tests was 19 713 during the study period: 20% were NIPT analyses (n = 3936) and 80% invasive procedures (n = 15 777). Twenty-five percent of NIPTs in the private clinics were performed before gestational week 11+0 , whereas NIPT in public settings was used only after combined first trimester screening (P < .001). Regardless of indication, the national public sensitivity was 96.9% (95% CI 82.0%-99.8%) for trisomy 21, 100% (95% CI 46.3%-100%) for trisomy 18, 100% (95% CI 5.5%-100%) for trisomy 13, and 87.0% (95% CI 74.5%-92.4%) for any fetal chromosomal aberration. Forty-seven true-positive NIPT results included cases of common aneuplodies (trisomy 21, n = 31; trisomy 18, n = 5; and trisomy 13, n = 1), sex chromosomal aberrations (n = 7) and atypical chromosomal aberrations (n = 3). One false-negative NIPT result occurred (trisomy 21). Of 47 cases, 21 (45%) cases with a true-positive NIPT result resulted in live births by choice; 11 of these children had Down and 4 had Edwards syndrome. CONCLUSIONS: The total number of NIPT analyses was low compared with the number of invasive procedures in the implementation period. In contrast to the generally high termination rate after a positive result following invasive testing in Denmark, a high proportion of true-positive NIPT results from the public setting resulted in live births. NIPT may be an important risk-free alternative to invasive testing for a minority of women in the public setting who wish to use prenatal genetic testing for information only and not for reproductive decision-making.
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Instalações de Saúde , Teste Pré-Natal não Invasivo/estatística & dados numéricos , Setor Privado , Setor Público , Adulto , Aberrações Cromossômicas , Dinamarca/epidemiologia , Síndrome de Down/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Sensibilidade e Especificidade , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomía do Cromossomo 18/diagnósticoRESUMO
PURPOSE: Gas station workers (GSWs) are exposed to carcinogenic agents. The aim was to study the association of high somatic chromosome alterations (CAs) rates in the blood of GSWs and the polymorphisms of three genes playing a role in DNA double-strand break repair. METHODS: This is a cross-sectional study with 114 GSWs and 115 age-matched controls. Cytogenetic analyses, blood exams, medical interviews and genotypes for RAD51/G135C (rs1801320), ATM/P1054R (rs1800057) and CHEK2/T470C (rs17879961) genes were performed. RESULTS: The CA rate in GSWs was 9.8 CAs/1000 metaphases, and 19.1% of the workers had > 10 CAs per 1000 metaphases (group two). GSWs had decreased levels of monocytes (P = 0.024) in their blood exams. The number of variant alleles of the RAD51/G135C polymorphism was higher in GSWs (P = 0.011) compared to the controls, and were associated with enhanced number of CAs per worker (P = 0.008). No allele variant was found for CHEK2/T470C in this study. CONCLUSION: The RAD51/G135C polymorphism appears to be related to genome instability in gas station workers. Increasing the knowledge of DNA repair gene variations involved in maintaining genomic stability in GSWs may be crucial for future cancer prevention.
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Aberrações Cromossômicas , Reparo do DNA/genética , Gasolina , Exposição Ocupacional , Rad51 Recombinase/genética , Adulto , Proteínas Mutadas de Ataxia Telangiectasia/genética , Brasil , Quinase do Ponto de Checagem 2/genética , Estudos Transversais , Feminino , Genótipo , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Indústria de Petróleo e Gás , Polimorfismo Genético , Adulto JovemRESUMO
In 2016 one person died and others had neurological sequelae during a clinical trial with BIA 10-2474 (3-(1-(cyclohexyl(methyl)carbamoyl)-lH-imidazol-4-yl)pyridine 1-oxide), a novel fatty acid amide hydrolase (FAAH) inhibitor being developed for the treatment of medical conditions such as pain. Prior to the clinical trial a full battery of regulatory toxicology tests were carried out and this paper describes the genotoxicity/mutagenicity tests undertaken with BIA 10-2474 using the Ames (Salmonella typhimurium) reverse mutation test, the Escherichia coli WP2uvrA forward mutation test, an in vitro chromosome damage assay in human lymphocytes, and an in vivo micronucleus test in mice. All tests were conducted with and without a rat liver S9 metabolic activation system. None of the test results were judged to be positive with regards to the mutagenicity/genotoxicity of BIA 10-2474 making it unlikely that any such effect was involved in the toxicity observed in the clinic.
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Antibacterianos/farmacologia , Óxidos N-Cíclicos/farmacologia , Inibidores Enzimáticos/farmacologia , Piridinas/farmacologia , Salmonella typhimurium/efeitos dos fármacos , Amidoidrolases/antagonistas & inibidores , Amidoidrolases/metabolismo , Animais , Células Cultivadas , Aberrações Cromossômicas , Feminino , Humanos , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Testes de Mutagenicidade , Ratos , Ratos Endogâmicos F344 , Salmonella typhimurium/genética , Salmonella typhimurium/metabolismoRESUMO
The potential genotoxic effect of venlafaxine hydrochloride (venlafaxine), an antidepressant drug-active ingredient, was investigated by using in vitro chromosome aberrations (CAs) and cytokinesis-block micronucleus (CBMN) assays in human peripheral blood lymphocytes (PBLs). Mitotic index (MI) and cytokinesis-block proliferation index (CBPI) were also calculated to determine the cytotoxicity of this active drug. For this aim, the human PBLs were treated with 25, 50, and 100 µg/ml venlafaxine for 24 h and 48 h. The results of this study showed that venlafaxine significantly induced the formation of structural CA and MN for all concentrations (25, 50, and 100 µg/ml) and treatment periods (24 h and 48 h) when compared with the negative and the solvent control (except 25 µg/ml at 48 h for MN). In addition, the increases in the percentage of structural CA and MN were concentration-dependent for both treatment times. With regard to cell cycle kinetics, venlafaxine significantly decreased the MI at all concentrations, and also CBPI at the higher concentrations for both treatment times as compared to the control groups. The present results indicate for the first time that venlafaxine had significant clastogenic and cytotoxic effects at the tested concentrations (25, 50, and 100 µg/ml) in the human PBLs, in vitro; therefore, its excessive and careless use may pose a potential risk to human health.
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Linfócitos/efeitos dos fármacos , Mutagênicos/toxicidade , Inibidores da Recaptação de Serotonina e Norepinefrina/toxicidade , Cloridrato de Venlafaxina/toxicidade , Adulto , Células Cultivadas , Aberrações Cromossômicas/induzido quimicamente , Relação Dose-Resposta a Droga , Feminino , Humanos , Linfócitos/patologia , Masculino , Testes para Micronúcleos , Índice Mitótico , Mutagênicos/administração & dosagem , Inibidores da Recaptação de Serotonina e Norepinefrina/administração & dosagem , Fatores de Tempo , Cloridrato de Venlafaxina/administração & dosagem , Adulto JovemRESUMO
Cerium (IV) oxide (CeO2), which is used as a biomaterial, has wide application in areas such as the biomedical, glass polishing, electronic, automotive, and pharmacology industries. Comparing with the literature, in this study, the genotoxic effects of cerium (IV) oxide microparticles (COMPs) and cerium (IV) oxide nanoparticles (CONPs) were investigated for the first time in human peripheral blood cultures at concentrations of 0.78, 1.56, 3.125, 6.25, 12.5, 25, and 50 ppm for 72 h under in vitro conditions. Particle sizes of COMPs and CONPs were determined using scanning electron microscopic analysis. Micronucleus and chromosome aberration tests were used to determine the genotoxicity of COMPs and CONPs. The average particle sizes of COMPs and CONPs were approximately 148.25 and 25.30 nm, respectively. It was determined that CeO2 particles in both micro and nano sizes were toxic at all concentrations compared to the negative control group (distilled water). Importantly, COMPs and CONPs were genotoxic even at the lowest concentration (0.78 ppm). Comparing particle sizes, the data indicated that COMPs were more toxic than CONPs. The results suggest that genotoxicity of COMPs and CONPs may be a function of applied concentrations and particle sizes.
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Cério/toxicidade , Aberrações Cromossômicas/efeitos dos fármacos , Cério/sangue , Humanos , Técnicas In Vitro , Testes para Micronúcleos , Testes de Mutagenicidade , Nanopartículas/toxicidade , Óxidos/toxicidade , Tamanho da PartículaRESUMO
Triflumuron (TFM) is an insect growth regulator (IGR), an insecticide commonly used over the world. It is known for its several toxic manifestations, such as reprotoxicity, immunotoxicity and hematotoxicity, which could affect public health. However, studies that reveal its toxic effects on mammalians are limited. To reach this purpose, our study aimed to elucidate the eventual genotoxic effects of TFM in mice bone marrow cells and in HCT 116 cells after a short term exposition. TFM was administered intraperitoneally to Balb/C male mice at doses of 250, 350 and 500 mg/kg bw for 24 h. Genotoxicity was monitored in bone marrow cells using the comet test, the micronucleus test and the chromosome aberration assay. Our results showed that TFM induced DNA damages in a dose-dependent manner. This genotoxicity was confirmed also in vitro on human intestinal cells HCT 116 using the comet test. It was then asked whether this genotoxicity induced by TFM could be due to an oxidative stress. Thus, we found that TFM significantly decreased HCT 116 cell viability. In addition, it induced the generation of reactive oxygen species (ROS) followed by lipid peroxidation as revealed by the increase in the malondialdehyde (MDA) levels. Similarly, the activation of the antioxidant enzymes (catalase and superoxide dismutase) was also observed. Our results indicated that, in our experimental conditions, TFM had a genotoxic effect on bone morrow cells and in HCT 116 cells. Moreover, we demonstrated that this genotoxicity passes through an oxidative stress.
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Benzamidas/toxicidade , Células da Medula Óssea/efeitos dos fármacos , Colo/efeitos dos fármacos , Dano ao DNA , Inseticidas/toxicidade , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Animais , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Sobrevivência Celular/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Ensaio Cometa , Células HCT116 , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Testes para Micronúcleos , Espécies Reativas de Oxigênio/metabolismoRESUMO
OBJECTIVE AND BACKGROUND: Chronic myeloid leukemia (CML) is a neoplastic disease whose genetic and cytogenetic changes play important roles in prognosis and treatment strategies. Philadelphia (Ph) translocation t(9;22)(q34;q11) is a diagnostic and prognostic biomarker in CML. METHODS: Pubmed and Google Scholar databases were searched for English language articles from 1975 to 2017 containing the terms CML; Additional chromosomal abnormalities; Philadelphia translocation; Prognosis; and Treatment. DISCUSSION: Approximately 10-12% of CML patients exhibit additional chromosomal aberrations (ACAs) in chronic phase and blast crisis. ACAs emergence may cause different features in CML patients according to Ph pattern. For instance, deletion of chromosome 9 derivation is associated to patient's bad survival, whereas monosomy 7 develops myeloid dysplastic syndrome (MDS) or acute myeloid leukemia (AML) in CML patients with Ph-negative pattern. And ACAs in Ph-positive CML is considered as a failure in the management of CML with imatinib. CONCLUSION: CML classification using different features such as Ph and ACAs can play a decisive role in the evaluation of treatment responses in patients, for example, CML patients with Ph negative and monosomy 7 develop MDS or CML patient -Y and extra copy of Ph have a good response to tyrosine kinase inhibitors, therefore, classifications according to Ph and ACAs play an important role in choosing better treatment protocols and therapeutic strategies. Karyotype analysis in CML patients with complex karyotype shows unrandom pattern so ACAs can be great clue in medical guidelines.
Assuntos
Aberrações Cromossômicas , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Cromossomo Filadélfia , Translocação Genética , Tomada de Decisão Clínica , Predisposição Genética para Doença , Humanos , Cariótipo , Cariotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Seleção de Pacientes , Fenótipo , Medicina de Precisão , Valor Preditivo dos Testes , PrognósticoRESUMO
Embryonic chromosome abnormalities are the most important causes of early spontaneous abortions. The aim of this study was to evaluate the spectrum and the frequencies of chromosomal anomalies in spontaneous miscarriages and to correlate these with maternal and gestational age. A retrospective study was conducted based on data obtained from a single medical genetics laboratory that collects cases from Western Romania. Long-term cultures of chorionic villus samples were established for karyotype analysis by GTG banding. Additionally, we performed QF-PCR to detect aneuploidies for chromosomes 13, 18, 21, X, and Y. In total, chorionic villi samples of 330 miscarriages (from August 2007 to November 2018) were analyzed. Results were obtained for 90.6% (299/330) of the cases. The remaining 9.4% (31/330) were excluded from evaluation due to inconclusive results. An abnormal karyotype was found in 156 cases (47.27%), while in 143 cases (43.33%) a normal karyotype was present. Of the abnormal cases, 88 (56.4%) had trisomies, 25 (16.0%) presented polyploidies, 25 (16.0%) had monosomy X, and 19 (11.5%) chromosome rearrangements. QF-PCR analysis identified aneuploidy in 2 out of 8 samples (25%). Cytogenetic investigations of spontaneous abortions provide valid data as to the cause of the abortion. This information may also be helpful for genetic counseling and considering future pregnancies.
Assuntos
Aborto Espontâneo/epidemiologia , Aborto Espontâneo/genética , Aberrações Cromossômicas/estatística & dados numéricos , Adolescente , Adulto , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
In response to the lack of authenticated mutagenicity/genotoxicity studies on MSG monohydrate, a series of genotoxicity studies conducted under GLP and according to globally accepted test guidelines (e.g., OECD) was performed. A bacterial reverse mutation test using Salmonella typhimurium (TA100, TA1535, TA98 and TA1537) and Escherichia coli (WP2 uvrA) at concentrations up to 5000 µg/plate, an in vitro chromosomal aberration test in CHL/IU cells at concentrations up to 10â¯mmol/L (1.9â¯mg/mL), a mouse lymphoma tk assay at concentrations up to 10â¯mmol/L (1.9â¯mg/mL), an in vitro micronucleus test in human peripheral blood lymphocytes at concentrations up to 10â¯mmol/L (1871⯵g/mL), and an in vivo micronucleus test in bone marrow of rats that were gavaged with up to 2000â¯mg/kg bw were investigated. MSG monohydrate did not cause mutagenicity in any bacterial strain, did not induce chromosomal aberrations in CHL/IU cells or gene mutation in mouse lymphoma cells, was not clastogenic or aneugenic to human lymphocytes, and did not induce micronuclei in erythrocytes of rats when compared with vehicle controls. These results show that MSG is not mutagenic or genotoxic under the study conditions.