Mutation Research. Genetic Toxicology and Environmental Mutagenesis

In this study, we used the cytokinesis-block micronucleus (CBMN) assay to evaluate the background frequency of cytogenetic damage in peripheral blood lymphocytes of the general population concerning different anthropometric data and lifestyle factors. The background frequency of CBMN assay parameters was analysed in 850 healthy, occupationally non-exposed male and female subjects (average age, 38±11 years) gathered from the general Croatian population from 2000 to 2023. The mean background values for micronuclei (MNi) in the whole population were 5...

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The risk of generating false positive in vivo comet assay results can be increased when procedural bias and/or technical variability is poorly controlled. This has been an ongoing concern since comet was first introduced into regulatory safety testing. But the proprietary nature of regulated studies and the 3Rs have limited the ability to conduct and publish the comparative in vivo studies necessary to determine the effect these factors can have on comet assay results when substances other than well characterized positive control compounds are evaluated in multiple tissues...

Type 2 diabetes mellitus (T2D) is a metabolic disease, which occurs largely due to unhealthy lifestyle. As oxidative stress is believed to promote T2D, by inducing damage to lipids, proteins, and DNA, appropriate dietary interventions seem critical to prevent, manage, and even reverse this condition. Brazil nuts (Bertholletia excelsa, H.B.K.) are nature's richest source of selenium, a mineral that has shown several health benefits. Therefore, this study aims to assess the effects of selenium consumption, through Brazil nuts, on biochemical and oxidative stress parameters, and genomic instability in T2D patients...

'Modern' oral tobacco-free nicotine pouches (NPs) are a nicotine containing product similar in appearance and concept to Swedish snus. A three-step approach was taken to analyse the biological effects of NPs and snus extracts in vitro. ToxTracker was used to screen for biomarkers for oxidative stress, cell stress, protein damage and DNA damage. Cytotoxicity, mutagenicity, and genotoxicity were assessed in the following respective assays: Neutral Red Uptake (NRU), Ames and Mouse Lymphoma Assay (MLA). Targeted analysis of phosphorylation signalling and inflammatory markers under non-toxic conditions was used to investigate any potential signalling pathways or inflammatory response...

The dosimetry and control of exposure for individuals chronically exposed to ionizing radiation are important and complex issues. Assessment may be optimized by evaluating individual adaptation and radiosensitivity, but it is not possible for a single model to account for all relevant parameters. Our goal was to develop approaches for the calculation of doses for persons chronically exposed to ionizing radiation, taking their radiosensitivities into consideration. On the basis of ex vivo radiation of blood samples, dose-effect models were constructed for dose ranges 0...

8-Hydroxydeoxyguanosine (8-OHdG) is well known not only as an effective biomarker of oxidative stress but also as a mutagenic DNA modification. Incorporation of dAMP at the opposite site of 8-OHdG induces G>T or A>C transversions. However, in vivo analyses of gene mutations caused by potassium bromate (KBrO3 ), which can induce 8-OHdG at carcinogenic target sites, showed that G>T was prominent in the small intestines of mice, but not in the kidneys of rats. Because KBrO3 was a much clearer carcinogen in the kidneys of rats, detailed analyses of gene mutations in the kidney DNA of rats treated with KBrO3 could improve our understanding of oxidative stress-mediated carcinogenesis...

DNA alterations in gametes, which may occur either spontaneously or as a result of exposure to genotoxicants, can lead to constitutional chromosomal anomalies in the offspring. Alcohol is an established genotoxicant. The goal of this hypothesis-testing longitudinal cohort study was to evaluate the effect of significant/sustained maternal alcohol exposure on clinically diagnosed constitutional chromosomal anomalies among children diagnosed with fetal alcohol syndrome (FAS). De-identified eligibility and claim healthcare records, prospectively generated from the 1990-2012 Florida Medicaid system within the Independent Healthcare Research Database (IHRD), were analyzed...

Preclinical and clinical studies have shown that molecular hydrogen (H2 ) has anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Safety data are available in the literature and acute toxicity has been tested in isolated cells and laboratory animals. We have evaluates the genotoxicity of H2 in vivo in rats after 72 h exposure, following the International Council for Harmonization guidelines ICH S2 (R1). The study was conducted on three groups of male Wistar rats: a negative control group, a positive control group receiving methyl methanesulfonate, and a H2 -treated group receiving a 3...

The ultraviolet (UV) component of sunlight can damage DNA. Although most solar UV is absorbed by the ozone layer, wavelengths > 300 nm (UVA and UVB bands) can reach the Earth's surface. It is essential to understand the genotoxic effects of UV light, particularly in natural environments. Caulobacter crescentus, a bacterium widely employed as a model for cell cycle studies, was selected for this study. Strains proficient and deficient in DNA repair (uvrA-) were used to concurrently investigate three genotoxic endpoints: cytotoxicity, SOS induction, and gene mutation, using colony-formation, the SOS chromotest, and RifR mutagenesis, respectively...

Arsenic is potent human carcinogen which affects millions of people across the globe. Arsenic induced pre-cancerous and cancerous skin lesions are hall marks of chronic arsenic toxicity. Even then, only 15%-20% of the population manifest arsenic-induced skin lesions but the rest do not, the reason for which in not very clear. Not only that, conjunctival irritations of the eyes, peripheral neuropathy and respiratory distress are the non-dermatological health effects which are often manifested in them in addition to the cancers of skin and other internal organs...

In this report we provide a summary of the presentations and discussion of the latest knowledge regarding the buccal micronucleus (MN) cytome assay. This information was presented at the HUMN workshop held in Malaga, Spain, in connection with the 2023 European, Environmental Mutagenesis and Genomics conference. The presentations covered the most salient topics relevant to the buccal MN cytome assay including (i) the biology of the buccal mucosa, (ii) its application in human studies relating to DNA damage caused by environmental exposure to genotoxins, (iii) the association of buccal MN with cancer and a wide range of reproductive, metabolic, immunological, neurodegenerative and other age-related diseases, (iv) the impact of nutrition and lifestyle on buccal MN cytome assay biomarkers; (v) its potential for application to studies of DNA damage in children and obesity, and (vi) the growing prospects of enhancing the clinical utility by automated scoring of the buccal MN cytome assay biomarkers by image recognition software developed using artificial intelligence...

5-Aminoisophthalic acid and 5-nitroisophthalic acid (5-NIPA) are potential impurities in preparations of 5-amino-2,4,6-triiodoisophthalic acid, which is a key intermediate in the synthesis of the iodinated contrast agent iopamidol. We have studied their mutagenicity in silico (quantitative structure-activity relationships, QSAR) and by the bacterial reverse mutation assay (Ames test). First, the compounds were screened with the tools Derek Nexus™ and Leadscope®. Both compounds were flagged as potentially mutagenic (class 3 under ICH M7)...

This study investigated N-nitrosomorpholine (NMOR) genotoxicity following UVA irradiation without metabolic activation. Following UVA irradiation, the photo treated NMOR (irradiated NMOR) was directly mutagenic, without UVA or metabolic activation, in the Ames test. The activity was relatively stable, and approximately 79% of the activity remained after 10 days of storage at 37 °C, 4 °C, or -20 °C. Micronuclei (MN) formation was observed in HaCaT cells after treatment with irradiated NMOR without metabolic activation...

The current study aimed to investigate genomic instabilities in healthcare workers who may experience varying levels of radiation exposure through various radiological procedures. It also sought to determine if factors related to the work environment and dosimeter reading could effectively explain the observed genomic instabilities. Utilizing the cytokinesis-block micronucleus assay (CBMN) on peripheral blood lymphocytes, we assessed a spectrum of genomic aberrations, including nucleoplasmic bridge (NPB), nuclear budding (NBUD), micronucleus (MN) formation, and total DNA damage (TDD)...

Potential genotoxicity is one of the essential considerations in the safety assessment of chemicals to which humans may be exposed. Several endpoints are used to evaluate genotoxicity, but, in each case, a binary assessment (negative/positive) is demanded by regulators. The use of binary assessment has rarely been questioned, although we have pointed out some questions and difficulties with regard to the statistical methods used and the evaluation of biological significance, both of which inform the calls of negative/ positive...

Sucrose and high-fructose corn syrup comprise nearly equal amounts of glucose and fructose. With the use of high-fructose corn syrup in the food industry, consumption of fructose, which may be a tumor promoter, has increased dramatically. We examined fructose-induced oxidative DNA damage in the presence of Cu(II), with or without the addition of H2 O2 . With isolated DNA, fructose induced Cu(II)-mediated DNA damage, including formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), to a greater extent than did glucose, and H2 O2 enhanced the damage...

The Ames MPF™ is a miniaturized, microplate fluctuation format of the Ames test. It is a standardized, commercially available product which can be used to assess mutagenicity in Salmonella and E. coli strains in 384-well plates using a color change-based readout. Several peer-reviewed comparisons of the Ames MPF™ to the Ames test in Petri dishes confirmed its suitability to evaluate the mutagenic potential of a variety of test items. An international multicenter study involving seven laboratories tested six coded chemicals with this assay using five bacterial strains, as recommended by the OECD test guideline 471...

Though telomeres play a crucial role in maintaining genomic stability in cancer cells and have emerged as attractive therapeutic targets in anticancer therapy, the relationship between telomere dysfunction and genomic instability induced by irradiation is still unclear. In this study, we identified that protection of telomeres 1 (POT1), a single-stranded DNA (ssDNA)-binding protein, was upregulated in γ-irradiated HeLa cells and in cancer patients who exhibit radiation tolerance. Knockdown of POT1 delayed the repair of radiation-induced telomeric DNA damage which was associated with enhanced H3K9 trimethylation and enhanced the radiosensitivity of HeLa cells...

The evaluation and interpretation of cytogenetic test data are discussed from the perspective of biological relevance. The reliability of tests must be considered, before evaluation and interpretation. Statistical procedures are important for the evaluation of test data, but for human health risk assessment, biological relevance is essential. Cell culture conditions must be carefully considered. Cells must be healthy in the physiologically controlled culture medium. Osmolality, pH, and temperature are critical factors in keeping the culture medium physiologically normal and avoiding artifactual responses...