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Find video protocols related to scientific articles indexed in Pubmed.
Assessment of the genotoxic and carcinogenic potentials of 3-aminothiophene derivatives using in vitro and in silico methodologies.
J Appl Toxicol
PUBLISHED: 07-17-2013
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Thiophene derivatives, a class of compounds widely used in products such as pharmaceuticals, agrochemicals or dyestuffs, represent chemicals of concern. Indeed, the thiophene ring is often considered as a structural moiety that may be involved in toxic effects in humans. We primarily focus on the genotoxic/mutagenic and carcinogenic potentials of the methyl 3-amino-4-methylthiophene-2-carboxylate (1), a precursor of the articaine local anesthetic (4) which falls within the scope of the European REACH (Registration, Evaluation, Authorisation and restriction of CHemicals) legislation. To discern some structure-toxicity relationships, we also studied two related compounds, namely the 3-amino 4-methylthiophene (2) and the 2-acetyl 4-chlorothiophene (3). Techniques employed to assess mutagenic and DNA-damaging effects involved the Salmonella mutagenicity assay (or Ames test) and the single-cell gel electrophoresis assay (or Comet assay). In the range of tested doses, none of these derivatives led to a positive response in the Ames tests and DNA damage was only observed in the Comet assay after high concentration exposure of 2. The study of their carcinogenic potential using the in vitro SHE (Syrian Hamster Embryo) cell transformation assay (CTA) highlighted the activity of compound 2. A combination of experimental data with in silico predictions of the reactivity of thiophene derivatives towards cytochrome P450 (CYP450), enabled us to hypothesize possible pathways leading to these toxicological profiles. Copyright © 2013 John Wiley & Sons, Ltd.
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Polycyclic aromatic hydrocarbons within airborne particulate matter (PM(2.5)) produced DNA bulky stable adducts in a human lung cell coculture model.
J Appl Toxicol
PUBLISHED: 06-20-2011
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To extend current knowledge on the underlying mechanisms of air pollution particulate matter (PM(2.5))-induced human lung toxicity, the metabolic activation of polycyclic aromatic hydrocarbons (PAH) within PM(2.5) and PAH-DNA bulky stable adduct patterns in human alveolar macrophage (AM) and/or human lung epithelial L132 cells in mono- and cocultures were studied. In the coculture system, only human AM were exposed to air pollution PM(2.5), unlike L132 cells. Particles, inorganic fraction and positive controls [i.e. TiO(2), thermally desorbed PM (dPM) and benzo[a]pyrene, B[a]P, respectively] were included in the experimental design. Cytochrome P450 (CYP) 1A1 gene expression, CYP1A1 catalytic activity and PAH-DNA bulky stable adducts were studied after 24, 48 and/or 72 h. Relatively low doses of PAH within PM(2.5) induced CYP1A1 gene expression and CYP1A1 catalytic activity in human AM and, thereafter, PAH-DNA bulky stable adduct formation. Adduct spots in PM(2.5) -exposed human AM were higher than those in dPM-exposed ones, thereby showing the incomplete removal of PAH by thermal desorption. PAH within air pollution PM(2.5) induced CYP1A1 gene expression but not CYP1A1 catalytic activity in L132 cells. However, despite the absence of PAH-DNA bulky stable adduct in L132 cells from human AM/L132 cell cocultures exposed to dPM(2.5) or PM(2.5), reliable quantifiable PAH-DNA bulky stable adducts were observed in L132 cells from human AM/L132 cell coculture exposed to B[a]P. Taken together, these results support the exertion of genotoxicity of highly reactive B[a]P-derived metabolites produced within human AM not only in primary target human AM, but also in secondary target L132 cells.
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DNA adduct variations in non-smoking crop farmers: potential relationship with occupational exposure to pesticides?
Environ. Toxicol. Pharmacol.
PUBLISHED: 01-18-2011
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Genotoxic impact of the occupational exposure was measured in farmers from Normandy, France. White blood cell DNA-adduct levels were measured for 116 non-smoking French crop farmers, using the (32)P-postlabelling method. A single blood sample was collected per farmer, at a randomised period of the year. Significantly higher bulky DNA-adduct levels were observed for samples collected from April to July, compared with samples collected during the other months. Agricultural practices were not significantly different between these two groups of farmers, but interestingly, the mean and the median duration without exposure to pesticides were significantly shorter for farmers sampled between April and July. These data, obtained in a homogeneous population of farmers, indicate a genotoxic impact for a sub-group, with a potential association with the use of pesticides. From the rest of the group, this study also gives for the first time additional information on the background fluctuations of this biomarker over the year.
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Benzo[a]pyrene, aflatoxine B? and acetaldehyde mutational patterns in TP53 gene using a functional assay: relevance to human cancer aetiology.
PLoS ONE
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Mutations in the TP53 gene are the most common alterations in human tumours. TP53 mutational patterns have sometimes been linked to carcinogen exposure. In hepatocellular carcinoma, a specific G>T transversion on codon 249 is classically described as a fingerprint of aflatoxin B(1) exposure. Likewise G>T transversions in codons 157 and 158 have been related to tobacco exposure in human lung cancers. However, controversies remain about the interpretation of TP53 mutational pattern in tumours as the fingerprint of genotoxin exposure. By using a functional assay, the Functional Analysis of Separated Alleles in Yeast (FASAY), the present study depicts the mutational pattern of TP53 in normal human fibroblasts after in vitro exposure to well-known carcinogens: benzo[a]pyrene, aflatoxin B(1) and acetaldehyde. These in vitro patterns of mutations were then compared to those found in human tumours by using the IARC database of TP53 mutations. The results show that the TP53 mutational patterns found in human tumours can be only partly ascribed to genotoxin exposure. A complex interplay between the functional impact of the mutations on p53 phenotype and the cancer natural history may affect these patterns. However, our results strongly support that genotoxins exposure plays a major role in the aetiology of the considered cancers.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.