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1.
Environ Anal Health Toxicol ; 38(2): e2023008-0, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37933102

RESUMO

Titanium dioxide (TiO2) was used in various applications in a wide range of products including food, cosmetics and photocatalyst. General toxicity studies of titanium dioxide, GST (Green Sludge Titanium) have been investigated in several reports, whereas studies concerning mutagenicity and genotoxicity have not been elucidated. Herein, we investigated the potential mutagenicity and genotoxicity of GST by genetic toxicology testing. The bacterial reverse mutation test was conducted by the pre-incubation method in the presence and absence of metabolic activation system (S9 mixture). The chromosome aberration test was performed using cultured Chinese hamster lung cell line in the absence and presence of S9 mixture. The micronucleus test was performed by using specific pathogen-free male ICR mice. Genotoxicity tests were conducted following the test guidelines of the Organisation for Economic Cooperation and Development with application of Good Laboratory Practice. No statistically significant increases were found in the bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test when tested for induction of genotoxicity in GST. These results suggest that GST did not induce mutagenicity and genotoxicity in both in vitro and in vivo system.

2.
Regul Toxicol Pharmacol ; 99: 238-243, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30268829

RESUMO

Eriobotrya japonica leaf is included in the Chinese Pharmacopoeia, and is widely used as a medicinal material in traditional medicine. The present study investigated the potential genotoxic effects of E. japonica leaf extract (EJE) using three standard battery systems. Genotoxicity tests were conducted following the test guidelines of the Organisation for Economic Cooperation and Development (OECD) and Ministry of Food and Drug Safety (MFDS), with application of Good Laboratory Practice. The bacterial reverse mutation test was conducted using the pre-incubation method in the presence or absence of the metabolic activation system (S9 mixture). The in vitro chromosome aberration test was performed using cultured Chinese hamster lung cell line in the presence or absence of the S9 mixture. The in vivo micronucleus test was performed using ICR mice. The bacterial reverse mutation test with Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 and Escherichia coli strain WP2uvrA showed that EJE did not induce gene mutations at any dose level in all the strains tested. EJE also did not show any chromosomal aberrations in the in vitro chromosomal aberration test and in the in vivo micronucleus test. These results showed that EJE did not induce mutagenicity or clastogenicity in either in vitro or in vivo systems.


Assuntos
Eriobotrya/toxicidade , Extratos Vegetais/toxicidade , Folhas de Planta/toxicidade , Animais , Linhagem Celular , Aberrações Cromossômicas/efeitos dos fármacos , Cricetinae , Cricetulus , Relação Dose-Resposta a Droga , Escherichia coli/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Testes para Micronúcleos/métodos , Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Mutação/efeitos dos fármacos , Salmonella typhimurium/efeitos dos fármacos
3.
Mol Cells ; 36(5): 410-6, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24218109

RESUMO

Caenorhabditis elegans, a cholesterol auxotroph, showed defects in larval development upon cholesterol starvation (CS) in a previous study. To identify cholesterol-responsive proteins likely responsible for the larval arrest upon CS, a comparative proteomic analysis was performed between C. elegans grown in normal medium supplemented with cholesterol (CN) and those grown in medium not supplemented with cholesterol (cholesterol starvation, CS). Our analysis revealed significant change (more than 2.2-fold, p < 0.05) in nine proteins upon CS. Six proteins were down-regulated [CE01270 (EEF-1A.1), CE08852 (SAMS-1), CE11068 (PMT-2), CE09015 (ACDH-1), CE12564 (R07H5.8), and CE09655 (RLA-0)], and three proteins were up-regulated [CE29645 (LEC-1), CE16576 (LEC-5), and CE01431 (NEX-1)]. RNAi phenotypes of two of the down-regulated genes, R07H5.8 (adenosine kinase) and rla-0 (ribosomal protein), in CN were similar to that of larval arrest in CS, and RNAi of a down-regulated gene, R07H5.8, in CS further enhanced the effects of CS, suggesting that down-regulation of these genes is likely responsible for the larval arrest in CS. All three up-regulated genes contain putative DAF-16 binding sites and mRNA levels of these three genes were all decreased in daf-16 mutants in CN, suggesting that DAF-16 activates expression of these genes.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/metabolismo , Colesterol/metabolismo , Animais , Anexinas/metabolismo , Sítios de Ligação , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Regulação para Baixo , Fatores de Transcrição Forkhead , Galectinas/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Larva/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Metilação , Fenótipo , Fosforilação , Proteômica , Genética Reversa , Transdução de Sinais/genética , Fatores de Transcrição/metabolismo , Regulação para Cima
4.
Mol Cells ; 31(2): 191-7, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21191815

RESUMO

ABSTEACT: IFE-1 is one of the five C. elegans homologs of eIF4E, which is the mRNA 5' cap-binding component of the translation initiation complex eIF4F. Depletion of IFE-1 causes defects in sperm, suggesting that IFE-1 regulates a subset of genes required for sperm functions. To further understand the molecular function of IFE-1, proteomic analysis was performed to search for sperm proteins that are downregulated in ife-1(ok1978); fem-3(q20) mutants relative to the fem-3(q20) control. The fem-3(q20) mutant background was used because it only produces sperm at restrictive temperature. Total worm proteins were subjected to 2D-DIGE, and differentially expressed protein spots were further identified by MALDI-TOF mass spectrometry. Among the identified proteins, GSP-3 and Major Sperm Proteins (MSPs) were found to be significantly down-regulated in the ife-1(ok1978) mutant. Moreover, RNAi of gsp-3 caused an ife-1-like phenotype. These results suggest that IFE-1 is required for efficient expression of some sperm-specific proteins, and the fertilization defect of ife-1 mutant is caused mainly by a reduced level of GSP-3.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Fator de Iniciação 4E em Eucariotos/química , Fatores de Iniciação em Eucariotos/metabolismo , Homologia de Sequência de Aminoácidos , Espermatozoides/metabolismo , Animais , Proteínas de Caenorhabditis elegans/genética , Regulação para Baixo , Eletroforese em Gel Bidimensional , Fatores de Iniciação em Eucariotos/genética , Masculino , Mutação/genética , Especificidade de Órgãos , Fenótipo , Proteômica , Interferência de RNA
5.
FEBS Lett ; 584(16): 3587-91, 2010 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-20647014

RESUMO

Treatment of Caenorhabditis elegans with apigenin, 5,7,4'-trihydroxyflavone, induces larval growth inhibition. To understand the molecular basis of apigenin-induced larval growth inhibition, the effects of apigenin on DAF-16 activity were examined. DAF-16 was activated through nuclear translocation and the mRNA level of sod-3, one of the known DAF-16 target genes, was increased upon apigenin treatment. DAF-16 activity was required for the growth inhibition, since the larval growth retardation upon apigenin treatment was suppressed in daf-16 mutants. These results indicate that apigenin acts as a stressor that activates DAF-16, which in turn inhibits larval growth.


Assuntos
Apigenina/farmacologia , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/metabolismo , Fatores de Transcrição/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Sequência de Bases , Caenorhabditis elegans/genética , Caenorhabditis elegans/crescimento & desenvolvimento , Proteínas de Caenorhabditis elegans/genética , Primers do DNA/genética , Fatores de Transcrição Forkhead , Genes de Helmintos , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Larva/metabolismo , Modelos Biológicos , Mutação , Fenótipo , RNA de Helmintos/genética , RNA de Helmintos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fatores de Transcrição/genética
6.
Dev Dyn ; 239(7): 1931-40, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20549717

RESUMO

C. elegans shows dauer-like larvae formation upon cholesterol starvation (CS), but the genetic epistasis among abnormal dauer formation (daf) genes during the process remains unclear. To clarify the genetic interactions among daf-9, daf-12, and daf-16 in this process, mRNA levels of these genes upon CS were measured. CS increased the mRNA levels of daf-9, daf-12, and daf-16. CS also induced DAF-16 nuclear localization, which was positively and negatively regulated by DAF-12 and DAF-9 activities, respectively. Activated DAF-16, a FOXO transcription factor, enhanced daf-12 but suppressed daf-9 expression, whereas DAF-9 inhibited daf-12 expression. Concomitantly, CS-induced larval arrest was regulated positively by DAF-12 and DAF-16, but negatively by DAF-9. The larval arrest in daf-9 mutant was suppressed by daf-12 RNAi, placing DAF-12 downstream of DAF-9. These results altogether suggest that circulatory mutual regulation among daf-9, daf-12, and daf-16 at the expression level mediates cholesterol signal to control larval development upon CS.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , Colesterol/farmacologia , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Larva/genética , Receptores Citoplasmáticos e Nucleares/genética , Fatores de Transcrição/genética , Animais , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/crescimento & desenvolvimento , Proteínas de Caenorhabditis elegans/metabolismo , Colesterol/deficiência , Fatores de Transcrição Forkhead , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/genética , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Mutação , Receptores Citoplasmáticos e Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Gênica/efeitos dos fármacos , Transcrição Gênica/genética
7.
Phys Med Biol ; 49(21): 4961-70, 2004 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-15584530

RESUMO

The purpose of this study was to improve the performance of a small gamma camera, utilizing a NaI(Tl) plate and a 5" position sensitive PMT. We attempted to build a NaI(Tl) plate crystal system which retained all its advantages, while at the same time integrating some of the advantages inherent in an array-type scintillation crystal system. Flood images were obtained with a lead hole mask, and position mapping was performed by detecting hole positions in the flood image. Energy calibration was performed using the energy spectra obtained from each hole position. Flood correction was performed using a uniformity correction table containing the relative efficiency of each image element. The spatial resolution was improved about 16% after correction at the centre field of view. Resolution deterioration at the outer field of view (OFOV) was considerably ameliorated, from 6.7 mm to 3.2 mm after correction. The sensitivity at the OFOV was also increased after correction, from 0.7 cps microCi(-1) to 2.0 cps microCi(-1). The correction also improved uniformity, from 5.2% to 2.1%, and linearity, from 0.5 mm to 0 mm. The results of this study indicate that the revised correction method can be employed to considerably improve the performance of a small gamma camera using a NaI(Tl) plate-type crystal. This method also provides high spatial resolution and linearity, like array-type crystals do, while retaining the specific advantages of plate-type crystals.


Assuntos
Análise de Falha de Equipamento , Câmaras gama , Aumento da Imagem/instrumentação , Tomografia por Emissão de Pósitrons/instrumentação , Cintilografia/instrumentação , Iodeto de Sódio/efeitos da radiação , Transdutores , Eletrônica Médica , Desenho de Equipamento , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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