Mutagenesis

http://mutage.oxfordjournals.org

List of Papers (Total 1,389)

Critical review of the current and future challenges associated with advanced in vitro systems towards the study of nanoparticle (secondary) genotoxicity

With the need to understand the potential biological impact of the plethora of nanoparticles (NPs) being manufactured for a wide range of potential human applications, due to their inevitable human exposure, research activities in the field of NP toxicology has grown exponentially over the last decade. Whilst such increased research efforts have elucidated an increasingly...

Genotoxicity of TiO2 nanoparticles assessed by mini-gel comet assay and micronucleus scoring with flow cytometry

The widespread production and use of nanoparticles calls for faster and more reliable methods to assess their safety. The main aim of this study was to investigate the genotoxicity of three reference TiO2 nanomaterials (NM) within the frame of the FP7-NANoREG project, with a particular focus on testing the applicability of mini-gel comet assay and micronucleus (MN) scoring by...

Diet-sourced carbon-based nanoparticles induce lipid alterations in tissues of zebrafish (Danio rerio) with genomic hypermethylation changes in brain

With rising environmental levels of carbon-based nanoparticles (CBNs), there is an urgent need to develop an understanding of their biological effects in order to generate appropriate risk assessment strategies. Herein, we exposed zebrafish via their diet to one of four different CBNs: C60 fullerene (C60), single-walled carbon nanotubes (SWCNT), short multi-walled carbon...

Toxicogenomics analysis of mouse lung responses following exposure to titanium dioxide nanomaterials reveal their disease potential at high doses

Titanium dioxide nanoparticles (TiO2NPs) induce lung inflammation in experimental animals. In this study, we conducted a comprehensive toxicogenomic analysis of lung responses in mice exposed to six individual TiO2NPs exhibiting different sizes (8, 20 and 300nm), crystalline structure (anatase, rutile or anatase/rutile) and surface modifications (hydrophobic or hydrophilic) to...

Surface modification does not influence the genotoxic and inflammatory effects of TiO2 nanoparticles after pulmonary exposure by instillation in mice

The influence of surface charge of nanomaterials on toxicological effects is not yet fully understood. We investigated the inflammatory response, the acute phase response and the genotoxic effect of two different titanium dioxide nanoparticles (TiO2 NPs) following a single intratracheal instillation. NRCWE-001 was unmodified rutile TiO2 with endogenous negative surface charge...

An in vitro study on the genotoxic effect of substituted furans in cells transfected with human metabolizing enzymes: 2,5-dimethylfuran and furfuryl alcohol

2,5-Dimethylfuran (DMF) and furfuryl alcohol (FFA) are two substituted furans that are formed during the processing of foods and have also been used as food flavorings. DMF and FFA are proposed to be bioactivated by human sulfotransferases (SULTs) which are not expressed in conventional cell lines used for genotoxicity testing. Therefore, in addition to the standard V79 cell line...

Genotoxicity of flubendazole and its metabolites in vitro and the impact of a new formulation on in vivo aneugenicity

The anti-parasitic benzimidazole flubendazole has been used for many years to treat intestinal infections in humans and animals. Previous genotoxicity studies have shown that the compound is not a bacterial mutagen and a bone marrow micronucleus test, using a formulation that limited systemic absorption, was negative. The purpose of this study is to explore the genotoxicity of...

Empirical analysis of BMD metrics in genetic toxicology part I: in vitro analyses to provide robust potency rankings and support MOA determinations

Genetic toxicity testing has traditionally been used for hazard identification, with dichotomous classification of test results serving to identify genotoxic agents. However, the utility of genotoxicity data can be augmented by employing dose–response analysis and point of departure determination. Via interpolation from a fitted dose–response model, the benchmark dose (BMD...

The clastogenicity of 4NQO is cell-type dependent and linked to cytotoxicity, length of exposure and p53 proficiency

4-Nitroquinoline 1-oxide (4NQO) is used as a positive control in various genotoxicity assays because of its known mutagenic and carcinogenic properties. The chemical is converted into 4-hydroxyaminoquinoline 1-oxide and gives rise to three main DNA adducts, N-(deoxyguanosin-8-yl)-4AQO, 3-(desoxyguanosin-N 2-yl)-4AQO and 3-(deoxyadenosin-N 6-yl)-4AQO. This study was designed to...

The utility of metabolic activation mixtures containing human hepatic post-mitochondrial supernatant (S9) for in vitro genetic toxicity assessment

In vitro genotoxicity assessment routinely employs an exogenous metabolic activation mixture to simulate mammalian metabolism. Activation mixtures commonly contain post-mitochondrial liver supernatant (i.e. S9) from chemically induced Sprague Dawley rats. Although Organization for Economic Cooperation and Development (OECD) test guidelines permit the use of other S9 preparations...

Genotoxic capacity of Cd/Se semiconductor quantum dots with differing surface chemistries

Quantum dots (QD) have unique electronic and optical properties promoting biotechnological advances. However, our understanding of the toxicological structure–activity relationships remains limited. This study aimed to determine the biological impact of varying nanomaterial surface chemistry by assessing the interaction of QD with either a negative (carboxyl), neutral...

Functional analysis of the new barley gene HvKu80 indicates that it plays a key role in double-strand DNA break repair and telomere length regulation

Genotoxic stress causes a reduced stability of the plant genome and has a detrimental effect on plant growth and productivity. Double-strand breaks (DSBs) are the most harmful of all DNA lesions because they cause the loss of genetic information on both strands of the DNA helix. In the presented study the coding and genomic sequences of the HvKu80 gene were determined. A...

The genome as a record of environmental exposure

Whole genome sequencing of human tumours has revealed distinct patterns of mutation that hint at the causative origins of cancer. Experimental investigations of the mutations and mutation spectra induced by environmental mutagens have traditionally focused on single genes. With the advent of faster cheaper sequencing platforms, it is now possible to assess mutation spectra in...

Metabolic profiling in human exposome studies

The human metabolome—the complement of small molecule metabolites present in biofluids and tissues—represents a significant part of the internal chemical milieu and is therefore an important aspect of the human exposome. Metabolic profiling approaches, commonly referred to as metabonomics or metabolomics, permit detailed and efficient characterisation of human biospecimens...

The exposome concept in a human nutrigenomics study: evaluating the impact of exposure to a complex mixture of phytochemicals using transcriptomics signatures

The application of transcriptome analyses in molecular epidemiology studies has become a promising tool in order to evaluate the impact of environmental exposures. These analyses have a great value in establishing the exposome, the totality of human exposures, both by identifying the chemical nature of the exposures and the induced molecular responses. Transcriptomic signatures...

Impact of exposure to wood dust on genotoxicity and cytotoxicity in exfoliated buccal and nasal cells

Wood dust was classified by the IARC as a human carcinogen which causes sinonasal tumours. However, the exposure in different industries varies strongly and the risks of workers depend on the specific situation which can be assessed by the use of biomonitoring methods. The aim of this study was to investigate the workers who are exposed to low dust levels (below the permitted...

Association between age and repair of oxidatively damaged DNA in human peripheral blood mononuclear cells

It has been hypothesised that positive associations between age and levels of oxidative stress-generated damage to DNA may be related to an age-dependent decline in DNA repair activity. The objective of this study was to investigate the association between age and repair activity of oxidatively damaged DNA in peripheral blood mononuclear cells (PBMCs). We isolated PBMCs from...

Sesamol attenuates genotoxicity in bone marrow cells of whole-body γ-irradiated mice

Ionising radiation causes free radical–mediated damage in cellular DNA. This damage is manifested as chromosomal aberrations and micronuclei (MN) in proliferating cells. Sesamol, present in sesame seeds, has the potential to scavenge free radicals; therefore, it can reduce radiation-induced cytogenetic damage in cells. The aim of this study was to investigate the radioprotective...

Formation of DNA adducts in wild-type and transgenic mice expressing human sulfotransferases 1A1 and 1A2 after oral exposure to furfuryl alcohol

Furfuryl alcohol (FFA) is present in many heat-treated foods as a result of its formation via dehydration of pentoses. It is also used legally as a flavouring agent. In an inhalation study conducted in the National Toxicology Program, FFA showed some evidence of carcinogenic activity in rats and mice. FFA was generally negative in conventional genotoxicity assays, which suggests...

No oxidative stress or DNA damage in peripheral blood mononuclear cells after exposure to particles from urban street air in overweight elderly

Exposure to traffic-related particulate matter (PM) has been associated with increased risk of lung disease, cancer and cardiovascular disease especially in elderly and overweight subjects. The proposed mechanisms involve intracellular production of reactive oxygen species (ROS), inflammation and oxidation-induced DNA damage studied mainly in young normal-weight subjects. We...

Cytotoxicity and genotoxicity of urban particulate matter in mammalian cells

Ambient air particulate matter (PM)-associated reactive oxygen species (ROS) have been linked to a variety of altered cellular outcomes. In this study, three different PM samples from diesel exhaust particles (DEPs), urban dust standard reference material SRM1649a and air collected in Manchester have been tested for their ability to oxidise DNA in a cell-free assay, to increase...

Micronucleus formation by single and mixed heavy metals/loids and PAH compounds in HepG2 cells

Humans and other organisms are exposed to multi-chemical mixtures including commonly found carcinogens such as polycyclic aromatic hydrocarbons (PAHs) and heavy metal/loids. The joint effects of these chemicals as beyond the binary mixtures have not been well characterised. In this study, we evaluated the combined genotoxicity of mixtures of PAHs and heavy metal/loids containing...

Structural chromosomal aberrations as potential risk markers in incident cancer patients

Epidemiological prospective studies have shown that increased chromosomal aberrations (CAs) in peripheral blood lymphocytes may predict cancer risk. Here, we report CAs in newly diagnosed 101 colorectal, 87 lung and 158 breast cancer patients and corresponding healthy controls. Strong differences in distributions of aberrant cells (ACs), CAs, chromatid-type aberrations (CTAs) and...

Oxidatively damaged DNA in the nasal epithelium of workers occupationally exposed to silica dust in Tuscany region, Italy

Chronic silica exposure has been associated to cancer and silicosis. Furthermore, the induction of oxidative stress and the generation of reactive oxygen species have been indicated to play a main role in the carcinogenicity of respirable silica. Therefore, we conducted a cross-sectional study to evaluate the prevalence of 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2...

Prevention of myelosuppression and genotoxicity induced by cisplatin in murine bone marrow cells: effect of an organovanadium compound vanadium(III)-l-cysteine

Cisplatin (CDDP) is one of the first-line anticancer drugs indicated for use against various form of human malignancies; but, the therapeutic outcome of CDDP chemotherapy is limited due to the development of myelosuppression and genotoxicity which may lead to secondary cancer. Induction of oxidative stress in normal host cells is thought to be responsible for these adverse...