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1.
SAR QSAR Environ Res ; 31(1): 33-48, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31766891

RESUMO

Over the past years, the European Food Safety Authority (EFSA) released to the public domain several databases, with the main objectives of collecting and storing hazard data on the substances considered in EFSA's risk assessment and secondly to serve as a basis for further development of in silico tools such as quantitative structure-activity relationship (QSAR) models. In this work, we evaluated the ability of freely available QSAR models to estimate genotoxicity and carcinogenicity properties and their possible use for screening purposes on three different EFSA's databases. With an accuracy close to 90%, the results showed good capabilities of QSAR models to predict genotoxicity in terms of bacterial reverse mutation test, while statistics for in vivo micronucleus test are not satisfactory (accuracy in the predictions close to 50%). Interestingly, results on the carcinogenicity assessment showed an accuracy in prediction close to 70% for the best models. In addition, an example of the potential application of in silico models is presented in order to provide a preliminary screening of genotoxicity properties of botanicals intended for use as food supplements.


Assuntos
Testes de Carcinogenicidade/estatística & dados numéricos , Testes de Mutagenicidade/estatística & dados numéricos , Relação Quantitativa Estrutura-Atividade , Bactérias/efeitos dos fármacos , Bactérias/genética , Bases de Dados Factuais , Testes para Micronúcleos/estatística & dados numéricos , Modelos Teóricos , Mutação/genética , Reprodutibilidade dos Testes , Medição de Risco
2.
Braz. J. Pharm. Sci. (Online) ; 54(1): e17292, 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-951918

RESUMO

It is understood that drugs regardless of their order of administration can exhibit drug interactions. Established on the fact that treatment of hypertension may last for decades and prolong usage of multiple drug regimen may induce substantial pathophysiological changes. Hence, This study was designed to evaluate the possible synergistic toxic effects of anti-hypertensive (carvedilol), and anti-inflammatory drug (celecoxib) alone and in combinations. Well-established MTT assay, Single Cell Gel Electrophoresis (SCGE) and Ames assay were employed to evaluate the toxicity at cellular level. Results from MTT assay on Vero cell line revealed that drug combinations have more pronounced anti-proliferative activity with combine IC50 value of 13.7:47.8 µg/mL. Likewise, exposure of peripheral blood mononuclear cells with drug combinations revealed significant (P<0.05) DNA damage (Class 3) in a dose dependent manner at concentrations ≥ 0.78: 2.34 µg/mL. However, carvedilol and celecoxib were non mutagenic against either mutant strain (TA 100 and TA 98) and combinations have also shown mild to moderate mutagenic potential. Nevertheless, upon addition of metabolic activation enzyme, concentration <12.5:37.5 µg/plate exhibited significant (P<0.05) mutagenicity against both tester strains. In conclusion, this study provides additional genotoxicity and mutagenicity data that could be used in considering options for formulating regimens with reduced mutagenic potential


Assuntos
Celecoxib , Anti-Inflamatórios/efeitos adversos , Testes de Mutagenicidade/estatística & dados numéricos , Anti-Hipertensivos/efeitos adversos , Genotoxicidade/análise , Hipertensão/fisiopatologia
4.
Mutat Res ; 809: 33-42, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27692297

RESUMO

A range of fibrous materials, including several types of asbestos and carbon fibres with nano scale diameters that had reported positive genotoxicity data (predominantly clastogenicity), were tested in the in vitro micronucleus test (OECD 487) in GLP-compliant studies in Chinese Hamster Ovary cells. Out of eight materials tested, only one (crocidolite, an asbestos fibre) gave a positive response either in the presence or absence of metabolic activation (S9) and at short (3h) or extended (24h) exposure times (p≤0.001). Our data suggest that the commonly used tests for clastogenicity in mammalian cells require extensive modification before fibrous materials are detected as positive, raising questions about the validity of these tests for detecting clastogenic and aneugenic fibrous materials.


Assuntos
Dano ao DNA/efeitos dos fármacos , Testes para Micronúcleos/métodos , Testes de Mutagenicidade/estatística & dados numéricos , Mutagênicos/toxicidade , Nanofibras/toxicidade , Animais , Asbestos/toxicidade , Células CHO , Carbono/toxicidade , Aberrações Cromossômicas/efeitos dos fármacos , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga , Testes de Mutagenicidade/métodos
5.
Regul Toxicol Pharmacol ; 76: 7-20, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26708083

RESUMO

The relative wealth of bacterial mutagenicity data available in the public literature means that in silico quantitative/qualitative structure activity relationship (QSAR) systems can readily be built for this endpoint. A good means of evaluating the performance of such systems is to use private unpublished data sets, which generally represent a more distinct chemical space than publicly available test sets and, as a result, provide a greater challenge to the model. However, raw performance metrics should not be the only factor considered when judging this type of software since expert interpretation of the results obtained may allow for further improvements in predictivity. Enough information should be provided by a QSAR to allow the user to make general, scientifically-based arguments in order to assess and overrule predictions when necessary. With all this in mind, we sought to validate the performance of the statistics-based in vitro bacterial mutagenicity prediction system Sarah Nexus (version 1.1) against private test data sets supplied by nine different pharmaceutical companies. The results of these evaluations were then analysed in order to identify findings presented by the model which would be useful for the user to take into consideration when interpreting the results and making their final decision about the mutagenic potential of a given compound.


Assuntos
Modelos Estatísticos , Mutagênese , Testes de Mutagenicidade/estatística & dados numéricos , Mutação , Relação Quantitativa Estrutura-Atividade , Algoritmos , Animais , DNA Bacteriano/efeitos dos fármacos , DNA Bacteriano/genética , Bases de Dados Factuais , Técnicas de Apoio para a Decisão , Humanos , Reprodutibilidade dos Testes , Medição de Risco , Software
6.
Acta toxicol. argent ; 23(2): 73-78, set. 2015. ilus, graf
Artigo em Espanhol | LILACS | ID: biblio-837840

RESUMO

El uso creciente de nanomateriales en productos industriales y de consumo ha incrementado la preocupación mundial respecto a sus posibles efectos adversos en los sistemas biológicos. Como consecuencia de la falta de un marco legislativo y la ausencia de un consenso sobre los protocolos experimentales, las investigaciones ecotoxicológicas se llevan a cabo a un ritmo mucho más lento que la producción de nuevas nanopartículas. Por esta razón, existe una necesidad creciente de realizar estudios que aporten conocimiento sobre el riesgo de estos contaminantes emergentes de propiedades únicas. El objetivo del presente trabajo fue evaluar la frecuencia de micronúcleos (FMN) en eritrocitos de ejemplares juveniles de pacú (Piaractus mesopotamicus) expuestos a nanopartículas de plata (Nano-Ag) a las concentraciones de 0 μg·L-1 (control); 2,5 μg·L-1; 10 μg·L-1; y 25 μg·L-1, durante 24 horas. Se observó que la FMN se incrementó significativamente (p<0,01) en la concentración de 25 μg·L-1, mientras que no hubo diferencias significativas entre los grupos expuestos a 2,5 y 10 μg·L-1 y el control. Estos resultados sugieren que los eventos aneugénicos o clastogénicos podrían representar un posible mecanismo de toxicidad de Nano-Ag en esta especie.


The growing use of nanomaterials in consumer and industrial products has aroused global concern about possible adverse effects on biological systems. Due to the lack of a regulation framework and the absence of a consensus on the experimental protocols, ecotoxicological investigations are carried out much slower than the production of new nanoparticles. For this reason, there is a growing need for studies that provide knowledge about the risk of these emerging contaminants of unique properties. The objective of the present study was to evaluate the frequency of micronuclei (FMN) in erythrocytes of juvenile Piaractus mesopotamicus exposed to silver nanoparticles (nano-Ag; Nanotek SA) at concentrations of 0 μg·L-1 (control); 2.5 μg·L-1; 10 μg·L-1; and 25 μg·L-1, for 24 hours (n = 10 per treatment). The FMN show a significant increase (p <0.01) in fish exposed to 25 μg·L-1 of Nano-Ag, while there were no significant differences among the groups exposed to 2.5 and 10 μg·L-1 with the control. These results suggest that the aneugenics or clastogenics events may represent a possible mechanism of toxicity of Nano-Ag in this specie.


Assuntos
Nanopartículas Metálicas/toxicidade , Testes para Micronúcleos/métodos , Microscopia Eletrônica de Transmissão/métodos , Testes de Mutagenicidade/estatística & dados numéricos
7.
Turk J Med Sci ; 45(3): 496-506, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26281312

RESUMO

BACKGROUND/AIM: Sexual dysfunction is a serious problem worldwide. In Turkey, herbal products are used by some people suffering from sexual dysfunction. Despite their therapeutic advantages, some constituents of herbs are potentially toxic and pose health risks because they can be bought from the market without a prescription. Therefore, we aimed to determine the safety of herbs possessing aphrodisiac effects, chosen on the basis of their frequency of medicinal use and commercial importance in Turkey. MATERIALS AND METHODS: Ten herbs (Anethum graveolens, Carthamus tinctorius, Citrus aurantium, Cocos nucifera, Glycyrrhiza glabra, Melissa officinalis, Nigella arvensis, Pinus pinea, Prunus mahaleb, and Zingiber officinale) were extracted with water, methanol, and chloroform. The cyto- and genotoxic potentials of the extracts were assessed using an MTT test on a rat kidney cell line and an Ames assay in Salmonella typhimurium strains, respectively. RESULTS: In the cytotoxic evaluation, IC50 values were 1.51-31.4 mg/mL for the methanol and chloroform extracts, while the water extracts were not cytotoxic. In the genotoxic evaluation, it was revealed that the water extracts had more mutagenic activity than the chloroform and methanol extracts. Water extract of M. officinalis was shown to have the most genotoxic activities to TA100 (±S9) and TA98 (-S9). CONCLUSION: These results might be useful in determining the toxic effects of herbs and lead to precautions being taken in regards to their consumption.


Assuntos
Afrodisíacos/farmacologia , Afrodisíacos/toxicidade , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Plantas Medicinais/toxicidade , Anethum graveolens/toxicidade , Animais , Carthamus tinctorius/toxicidade , Células Cultivadas , Citrus/toxicidade , Cocos/toxicidade , Gengibre/toxicidade , Glycyrrhiza/toxicidade , Rim , Melissa/toxicidade , Testes de Mutagenicidade/estatística & dados numéricos , Nigella/toxicidade , Pinus/toxicidade , Prunus/toxicidade , Ratos , Turquia
8.
Acta toxicol. argent ; 21(1): 5-14, jun. 2013.
Artigo em Espanhol | LILACS | ID: lil-694580

RESUMO

Un factor decisivo de la Revolución Verde ha sido el desarrollo y aplicación de plaguicidas para combatir una gran variedad de organismos considerados perjudiciales por el hombre, que afectan la productividad de los cultivos de interés agronómico. Sin embargo, el incremento sostenido del uso de pesticidas trajo aparejado un aumento de la presencia de los mismos en el ambiente, llegando a afectar a los ecosistemas y a la salud humana. La exposición de las poblaciones a plaguicidas, se da en forma de mezclas complejas, tanto por la aplicación de distintos plaguicidas en simultáneo como por la presencia de aditivos en las formulaciones comerciales. Teniendo en cuenta la producción científica relacionada en los últimos años, el objetivo de este trabajo fue evaluar los avances sobre la genotoxicidad de pesticidas y sus mezclas, en concentraciones similares a las encontradas en el ambiente. Además, dada la complejidad de los estudios de monitoreo y la imposibilidad de establecer correlaciones directas, se propone reconocer la utilidad de los ensayos de corto plazo en niveles de evaluación de menor complejidad como una aproximación al contexto real.


A crucial factor of the Green Revolution has been the development and application of pesticides to prevent the potential harm of a variety of organisms that affect crop yields of agronomic interest. However, the sustained increase in the use of these compounds resulted in an enhancement of their presence in the environment, affecting ecosystems and human health. Populations are exposed to complex pesticide mixtures because they are usually combined and commercial formulations content several additives. Considering the scientifc output on the subject in recent years, the aim of this work is to evaluate advancement on the genotoxicity of pesticides and their mixtures at similar concentrations to those found in the environment. Moreover, given the complexity of monitoring studies and the lack of certainty to establish direct correlations, it is proposed to recognize the applicability of short-term tests of minor complexity as an approximation to the real context.


Assuntos
Biomarcadores Ambientais , Genotoxicidade , Praguicidas/toxicidade , Testes de Mutagenicidade/estatística & dados numéricos
9.
Toxicol In Vitro ; 27(4): 1312-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23499632

RESUMO

In vitro genotoxicity assays are often used to compare tobacco smoke particulate matter (PM) from different cigarettes. The quantitative aspect of the comparisons requires appropriate statistical methods and replication levels, to support the interpretation in terms of power and significance. This paper recommends a uniform statistical analysis for the Ames test, mouse lymphoma mammalian cell mutation assay (MLA) and the in vitro micronucleus test (IVMNT); involving a hierarchical decision process with respect to slope, fixed effect and single dose comparisons. With these methods, replication levels of 5 (Ames test TA98), 4 (Ames test TA100), 10 (Ames test TA1537), 6 (MLA) and 4 (IVMNT) resolved a 30% difference in PM genotoxicity.


Assuntos
Testes de Mutagenicidade/estatística & dados numéricos , Material Particulado/toxicidade , Fumaça/efeitos adversos , Tabaco , Animais , Linhagem Celular , Interpretação Estatística de Dados , Camundongos , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética
10.
Basic Clin Pharmacol Toxicol ; 112(5): 302-13, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23374861

RESUMO

This survey is a compendium of genotoxicity and carcinogenicity information of bronchodilators and antiasthma drugs. Data from 46 marketed drugs were collected. Of these 46 drugs, 25 (54.3%) did not have retrievable genotoxicity or carcinogenicity data. The remaining 21 (45.7%) had at least one genotoxicity or carcinogenicity test result. Of these 21 drugs, 10 had at least one positive finding: three tested positive in at least one genotoxicity assay, eight in at least one carcinogenicity assay, and one of them gave positive results in both genotoxicity assay and carcinogenicity assay. Concerning the predictivity of genetic toxicology findings for the result(s) of long-term carcinogenesis assays, 15 drugs had both genotoxicity and carcinogenicity data: seven of them (46.6%) were neither genotoxic nor carcinogenic, 6 (40.0%) were carcinogenic in at least one sex of mice or rats but tested negative in genotoxicity assays, 1 (6.7%) tested positive in genotoxicity assay but was non-carcinogenic, and 1 (6.7%) gave positive responses in both genotoxicity and carcinogenicity assay. Only 11 (23.9%) of the 46 drugs considered had all data required by current guidelines for testing of pharmaceuticals, but a large fraction of them were developed and marketed prior to the present regulatory climate.


Assuntos
Broncodilatadores/toxicidade , Testes de Carcinogenicidade , Carcinógenos/toxicidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Testes de Mutagenicidade , Mutagênicos/toxicidade , Animais , Testes de Carcinogenicidade/estatística & dados numéricos , Carcinógenos/classificação , Coleta de Dados , Guias como Assunto , Camundongos , Testes de Mutagenicidade/estatística & dados numéricos , Mutagênicos/classificação , Preparações Farmacêuticas/classificação , Ratos
12.
J Chem Inf Model ; 52(11): 2840-7, 2012 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-23030379

RESUMO

Mutagenicity is one of the most important end points of toxicity. Due to high cost and laboriousness in experimental tests, it is necessary to develop robust in silico methods to predict chemical mutagenicity. In this paper, a comprehensive database containing 7617 diverse compounds, including 4252 mutagens and 3365 nonmutagens, was constructed. On the basis of this data set, high predictive models were then built using five machine learning methods, namely support vector machine (SVM), C4.5 decision tree (C4.5 DT), artificial neural network (ANN), k-nearest neighbors (kNN), and naïve Bayes (NB), along with five fingerprints, namely CDK fingerprint (FP), Estate fingerprint (Estate), MACCS keys (MACCS), PubChem fingerprint (PubChem), and Substructure fingerprint (SubFP). Performances were measured by cross validation and an external test set containing 831 diverse chemicals. Information gain and substructure analysis were used to interpret the models. The accuracies of fivefold cross validation were from 0.808 to 0.841 for top five models. The range of accuracy for the external validation set was from 0.904 to 0.980, which outperformed that of Toxtree. Three models (PubChem-kNN, MACCS-kNN, and PubChem-SVM) showed high and reliable predictive accuracy for the mutagens and nonmutagens and, hence, could be used in prediction of chemical Ames mutagenicity.


Assuntos
Simulação por Computador , Testes de Mutagenicidade/métodos , Mutagênicos/química , Mutagênicos/toxicidade , Animais , Teorema de Bayes , Bases de Dados de Compostos Químicos , Árvores de Decisões , Humanos , Testes de Mutagenicidade/estatística & dados numéricos , Valor Preditivo dos Testes , Relação Quantitativa Estrutura-Atividade , Reprodutibilidade dos Testes , Máquina de Vetores de Suporte
13.
Environ Mol Mutagen ; 53(3): 185-97, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22246666

RESUMO

An international round-robin study on the Ames fluctuation test [ISO 11350, 2012], a microplate version of the classic plate-incorporation method for the detection of mutagenicity in water, wastewater and chemicals was performed by 18 laboratories from seven countries. Such a round-robin study is a precondition for both the finalization of the ISO standardization process and a possible regulatory implementation in water legislation. The laboratories tested four water samples (spiked/nonspiked) and two chemical mixtures with and without supplementation of a S9-mix. Validity criteria (acceptable spontaneous and positive control-induced mutation counts) were fulfilled by 92-100%, depending on the test conditions. A two-step method for statistical evaluation of the test results is proposed and assessed in terms of specificity and sensitivity. The data were first subjected to powerful analysis of variance (ANOVA) after an arcsine-square-root transformation to detect significant differences between the test samples and the negative control (NC). A threshold (TH) value based on a pooled NC was then calculated to exclude false positive test results. Statistically, positive effects observed by the William's test were considered negative, if the mean of all replicates of a sample did not exceed the calculated TH. By making use of this approach, the overall test sensitivity was 100%, and the test specificity ranged from 80 to 100%.


Assuntos
Testes de Mutagenicidade/métodos , Testes de Mutagenicidade/normas , Resíduos , Poluentes Químicos da Água/toxicidade , Animais , Masculino , Testes de Mutagenicidade/estatística & dados numéricos , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Salmonella/efeitos dos fármacos , Salmonella/genética
14.
Pharm Stat ; 10(6): 477-84, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22140058

RESUMO

The Statisticians in the Pharmaceutical Industry Toxicology Special Interest Group has collated and compared statistical analysis methods for a number of toxicology study types including general toxicology, genetic toxicology, safety pharmacology and carcinogenicity. In this paper, we present the study design, experimental units and analysis methods.


Assuntos
Projetos de Pesquisa/estatística & dados numéricos , Toxicologia/normas , Animais , Testes de Carcinogenicidade/estatística & dados numéricos , Feminino , Masculino , Testes de Mutagenicidade/estatística & dados numéricos , Testes de Toxicidade/estatística & dados numéricos
16.
Regul Toxicol Pharmacol ; 56(1): 1-3, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19782117

RESUMO

Genotoxicity testing is an important part of preclinical safety assessment of new drugs and is required prior to Phase I/II clinical trials. It is designed to detect genetic damage such as gene mutations and chromosomal aberration, which may be reflected in tumorigenic or heritable mutation potential of the drug. Botanical new drugs in the U.S. are entitled to a waiver for preclinical pharmacology/toxicology studies, including genotoxicity testing, in support of an initial clinical trial under IND, contingent on previous human experience. Recently, ethical concerns have been raised over conducting Phase I/II clinical trials of new drugs with positive genotoxicity findings in healthy volunteers. Although the relevance of this issue to patients, as opposed to healthy volunteers, depends on the drug's indication, duration of treatment, and specific findings related to the assays, the regulatory view is to avoid exposing patients to genotoxic compounds unnecessarily in clinical trials. This philosophy may impact on herbal supplement marketing and botanical drug development, in that genotoxicity data are often lacking while consumers are exposed to the herbal supplement, or healthy volunteers are tested in an initial Phase I/II clinical trial on the botanical drug. This paper presents results of a survey conducted on genotoxicity data in botanical INDs submitted to the Agency and discusses the significance of this information. The information presented indicates that the sponsors of botanical INDs have increasingly recognized the importance of genotoxicity information and may have prioritized its acquisition in their strategic drug development programs.


Assuntos
Aprovação de Drogas/estatística & dados numéricos , Drogas em Investigação/toxicidade , Aplicação de Novas Drogas em Teste/estatística & dados numéricos , Preparações de Plantas/toxicidade , Experimentação Humana Terapêutica , Ensaios Clínicos como Assunto/estatística & dados numéricos , Humanos , Testes de Mutagenicidade/estatística & dados numéricos , Estados Unidos
17.
Mutagenesis ; 25(1): 17-23, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19892773

RESUMO

Hair dye ingredients frequently produce positive results in short-term in vitro genotoxicity tests, although results from in vivo assays are typically negative, especially for ingredients in use today. The use of hair dyes is quite widespread resulting in the exposure both for persons working in hairdressing salons and for individuals who have their hair dyed. This provides the opportunity to add to the data from standard in vitro and in vivo genotoxicity tests by investigating whether or not genotoxic responses are detected in such exposed individuals. A number of biomonitoring studies of humans exposed to hair dyes have been conducted using either cytogenetic alterations or DNA damage as measures of genotoxicity, or urine mutagenicity as a measure of exposure to genotoxic compounds. In this paper, each study is critically reviewed and interpreted. Overall, there is no consistent evidence of genotoxicity in humans exposed to hair dyes occupationally or through individual use.


Assuntos
Dano ao DNA/genética , Monitoramento Ambiental/estatística & dados numéricos , Tinturas para Cabelo/toxicidade , Exposição Ocupacional/estatística & dados numéricos , Humanos , Testes de Mutagenicidade/estatística & dados numéricos , New York
18.
Toxicol Lett ; 190(3): 298-302, 2009 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-19857797

RESUMO

EMS induced micronuclei and lacZ mutations in in vivo studies in mice with a clearly sublinear dose dependency. As reported elsewhere in this issue, NOEL dose values of between 25 mg/kg/day and 80 mg/kg/day were observed for the different endpoints and tissues analysed. Here we show that statistical assessment of the data provides solid support that the induction of mutagenic and clastogenic effects after in vivo treatment with the directly DNA damaging mutagen EMS adheres to a thresholded dose response relation. These data corroborate similar evidence obtained in in vitro studies. We conclude that cells are fully capable of repairing large amounts of DNA ethylations induced by EMS without experiencing elevated mutation frequencies. The stochastic, linear risk assessment model generally employed for DNA damaging genotoxins can therefore be refuted for EMS. While presently this conclusion cannot be generalized to other genotoxins a change of paradigm appears to be indicated at least for alkylating agents inducing a comparable type and spectrum of DNA lesions as EMS.


Assuntos
Alquilantes/toxicidade , Contaminação de Medicamentos , Óperon Lac/efeitos dos fármacos , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Mutagênicos/toxicidade , Mutação/efeitos dos fármacos , Animais , Intervalos de Confiança , DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Metanossulfonato de Etila/toxicidade , Inibidores da Protease de HIV/química , Humanos , Modelos Lineares , Camundongos , Testes de Mutagenicidade/estatística & dados numéricos , Nelfinavir/química , Nível de Efeito Adverso não Observado , Medição de Risco/estatística & dados numéricos
19.
Mutat Res ; 661(1-2): 101-9, 2009 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-19100753

RESUMO

Fluctuation analysis is an established and widely used technique of estimating mutation rates in cultured cells. This paper presents a modified median estimator of mutation rates, which is novel because it allows for unequal population sizes N(t) of the parallel cultures, and helps to detect and reduce the estimation variability. Simulation results show a good accuracy and robustness of the modified median estimator compared with the median estimator and the maximum likelihood estimator. The proposed estimator, based on the Luria-Delbrück model, is applied to 20 yeast datasets collected during 3 different days for a study of chromosome loss and recombination in wild-type Saccharomyces cerevisiae strains. The estimates obtained display among-experiment variability, which is inflated with respect to the model predictions on simulated data. Further investigation in S. cerevisiae and Escherichia coli uncovers an empirical inverse relationship between the population sizes N(t) and the mutation rate estimates under certain experimental conditions. The impact of these effects on the practice of fluctuation analysis is discussed.


Assuntos
Modelos Genéticos , Testes de Mutagenicidade/estatística & dados numéricos , Mutação , Aneuploidia , Contagem de Colônia Microbiana , Intervalos de Confiança , Bases de Dados Genéticas , Escherichia coli/genética , Genes Fúngicos , Funções Verossimilhança , Método de Monte Carlo , Recombinação Genética , Saccharomyces cerevisiae/genética
20.
Arch. prev. riesgos labor. (Ed. impr.) ; 11(3): 124-130, jul.-sept. 2008. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-66571

RESUMO

Objetivo. Evaluar los efectos genotóxicos e inmunotóxicos asociados a la exposición laboral al plomo.Métodos. Se ha realizado el ensayo de mutación en el receptor de las células T (TCR) y se han determinado las variacionesen los porcentajes de diferentes subpoblaciones linfocitarias y en las concentraciones de ciertas citoquinas circulantesen plasma sanguíneo mediante citometría de fl ujo en 30 trabajadores expuestos procedentes de 2 empresas y en 30 trabajadoresno expuestos como grupo control.Resultados: Los individuos expuestos mostraron frecuencias de mutación signifi cativamente mayores que los controles(media±error estándar: 20,88±3,58 vs. 12,98±2,88), independientemente de su empresa de procedencia, así como menorporcentaje de linfocitos CD8+ (%medio±error estándar: 31,97±1,70 vs. 36,70±1,30), descenso que sólo mantuvo signifi caciónen una de las empresas. Las concentraciones de las citoquinas analizadas fueron en general mayores en los expuestosque en los controles, siendo signifi cativo el incremento para IL-2 (media±error estándar: 1,09±0,26 vs. 0,25±0,17 pg/ml)e IL-10 (media±error estándar: 2,88±1,14 vs. 0,58±0,23 pg/ml), con diferencias entre empresas. Los efectos de la exposiciónen cuanto a frecuencia de mutación y concentraciones de IL-2 e IL-10 fueron mayores en los individuos no fumadores,apuntando a una menor susceptibilidad de los fumadores posiblemente como consecuencia de la potenciación de los mecanismosde reparación por el contacto crónico con el humo del tabaco.Conclusiones. Los resultados indican que la exposición laboral a plomo induce mutagenicidad y alteraciones en parámetrosinmunológicos, sugiriendo la necesidad de aplicación de medidas para la eliminación o disminución de los nivelesde plomo en los lugares de trabajo


Objective. To evaluate genotoxic and immunotoxic effects associated with occupational exposure to lead.Methods. A T-cell receptor (TCR) mutation assay was performed, and variations in the percentages of different lymphocytesubpopulations and in the concentrations of certain plasma circulating cytokines determined by fl ow cytometry in30 exposed individuals from 2 factories and 30 controls.Results. Exposed individuals showed signifi cantly higher levels of mutation frequency than controls (mean±standard error:20.88±3.58 vs. 12.98±2.88), regardless of their factory; the percentage of CD8+ lymphocytes was also lower (mean%±standard error: 31.97±1.70 vs. 36.70±1.30), although statistical signifi cance was observed in only one factory. Concentrations ofanalysed cytokines were generally higher among exposed individuals than controls. The increase was signifi cant for IL-2(mean±standard error: 1.09±0.26 vs. 0.25±0.17) and IL-10 (mean±standard error: 2.88±1.14 vs. 0.58±0.23), with differencesbetween factories. Exposure effects regarding mutation frequency and IL-2 and IL-10 concentrations were greater amongnonsmokers, suggesting a lower susceptibility of smokers as a consequence of strengthening of repair mechanisms throughchronic contact with tobacco smoke.Conclusions. Occupational exposure to lead induces mutagenicity and alterations in immunological parameters, suggestingthe need to apply measures for the elimination or decrease of lead levels in workplaces


Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Intoxicação por Chumbo/diagnóstico , Intoxicação por Chumbo/epidemiologia , Linfócitos T/efeitos da radiação , Saúde do Trabalhador/estatística & dados numéricos , Riscos Ocupacionais/estatística & dados numéricos , Citometria de Fluxo/métodos , Biomarcadores/análise , Análise de Variância , Chumbo/efeitos adversos , Chumbo/toxicidade , Intoxicação por Chumbo/fisiopatologia , Testes de Mutagenicidade/estatística & dados numéricos
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