Sechium edule (Jacq.) Swartz is a perennial herbaceous climbing plant with tendrils and tuberous roots belonging to the Cucurbitaceae family. Its fruits (\"chayote\"), stems, roots, and leaves are edible and are commonly ingested by humans. It has shown medicinal properties attributed to its bioactive compounds (vitamins, phenolic acids, flavonoids, carotenoids, triterpenoids, polyphenolic compounds, phytosterols, and cucurbitacins), which together have been associated with the control and prevention of chronic and infectious diseases, highlighting its antibacterial, anti-cardiovascular/antihypertensive, antiepileptic, anti-inflammatory, hepatoprotective, antiproliferative, and antioxidant activities. The objective of the study was to determine the antigenotoxic potential of two types of fresh chayote juice (filtered (FChJ) and unfiltered (UFChJ)) against DNA damage produced by benzo[a]pyrene (B[a]P) using an in vivo mouse peripheral blood micronucleus assay (MN). The juices were consumed freely for 2 weeks. A negative control, a control group of each juice, a positive batch [B[a]P], and two combined batches (B[a]P plus FChJ or UFChJ) were included. Blood smears were stained and observed under a microscope to quantify the number of micronucleated normochromic erythrocytes (MNNEs). The results indicate: (a) B[a]P increased the frequency of MNNEs and reduced the rate of PEs; and (b) no juice produced toxic effects or induced MN. On the contrary, both juices were genoprotective. However, the most significant effect was presented by UFChJ at the end of the experiment (70%). It is suggested that UFChJ has a greater amount of fiber and/or phytochemicals that favor the therapeutic effect. Possibly, the genoprotection is also related to its antioxidant capacity.

To better understand the mechanism of action of the compounds in the ethanolic extracts of J. nigra leaves and green husks, their binding to CT-DNA was investigated. This study was conducted to elucidate the in vitro protective effect of extracts against chromosomal damage in mitogen-induced human lymphocytes and investigate the possible application of selec+ted extracts as a natural source of polyphenolic compounds. Using HPLC-MS analysis, 103 different compounds were identified as having a higher number of active species, which is consistent with their activity. The frequency of micronuclei (MN) was scored in binucleated cells, and the nuclear proliferation index was calculated. Cyclic voltammetry experiments demonstrate that the nature of the interaction between extracts and CT-DNA is a synergy of electrostatic and intercalative modes, where leaves extracts showed a higher ability to bind to DNA. Extracts showed excellent antioxidant activity. At a concentration of only 4 µg/mL, extract of J. nigra leaves and the green husks reduced the incidence of MN by 58.2% and 64.5%, respectively, compared to control cell cultures.

OBJECTIVE: Undernutrition is a serious health problem prevalent in poor countries, affecting millions of people worldwide, especially young children, pregnant women, and sick elderly individuals. This condition increases vulnerability to infections, leading to widespread use of antibiotic treatments in undernourished populations. The objective of the present study was to determine the in vivo genotoxic and cytotoxic effects of trimethoprim-sulfamethoxazole (TMP-SMX) treatment according to nutritional conditions.
METHODS: The effects of TMP-SMX treatment were measured by analyzing the kinetics of micronucleated reticulocytes (MN-RET) induced in the peripheral blood of young, well-nourished (WN) and undernourished (UN) rats.
RESULTS: In the WN group, two distinct peaks of MN-RET were observed, while the UN group had a significantly higher basal frequency of MN-RET compared to the WN group and only a later peak. Reticulocyte (RET) frequency slightly decreased in WN, indicating a poor cytotoxic effect. In contrast, in the UN, the treatment caused a significant increase in RET frequency. The results indicate that SMX\'s aromaticity index decreases when formed with TMP, suggesting potentially fewer toxic effects.
CONCLUSIONS: In vivo TMP-SMX produces two MN-RET induction peaks in WN animals, indicating two DNA damage induction mechanisms and consequent micronucleus production. The UN rats did not display the two peaks, indicating that the first MN induction mechanism did not occur in UN, possibly due to pharmacokinetic effects, decreased metabolism or effects on cell proliferation. TMP-SMX has a slight cytotoxic effect on WN. In contrast, in the UN, the antibiotic treatment seems to favor early erythropoiesis.

Chemical safety testing plays a crucial role in product and pharmacological development, as well as chemoprevention; however, in vitro genotoxicity safety tests do not always accurately predict the chemicals that will be in vivo carcinogens. If chemicals test positive in vitro for genotoxicity but negative in vivo, this can contribute to unnecessary testing in animals used to confirm erroneous in vitro positive results. Current in vitro tests typically evaluate only genotoxicity endpoints, which limits their potential to detect non-genotoxic carcinogens. The frequency of misleading in vitro positive results can be high, leading to a requirement for more informative in vitro tests. It is now recognized that multiple-endpoint genotoxicity testing may aid more accurate detection of carcinogens and non-carcinogens. The objective of this review was to evaluate the utility of our novel, multiple-endpoint in vitro test, which uses multiple cancer-relevant endpoints to predict carcinogenic potential. The tool assessed micronucleus frequency, p53 expression, p21 expression, mitochondrial respiration, cell cycle abnormalities and, uniquely, cell morphology changes in human lymphoblastoid cell lines, TK6 and MCL-5. The endpoints were used to observe cellular responses to 18 chemicals within the following categories: genotoxic carcinogens, non-genotoxic carcinogens, toxic non-carcinogens, and misleading in vitro positive and negative agents. The number of endpoints significantly altered for each chemical was considered, alongside the holistic Integrated Signature of Carcinogenicity score, derived from the sum of fold changes for all endpoints. Following the calculation of an overall score from these measures, carcinogens exhibited greater potency than non-carcinogens. Genotoxic carcinogens were generally more potent than non-genotoxic carcinogens. This novel approach therefore demonstrated potential for correctly predicting whether chemicals with unknown mechanism may be considered carcinogens. Overall, while further validation is recommended, the test demonstrates potential for the identification of carcinogenic compounds. Adoption of the approach could enable reduced animal use in carcinogenicity testing.

OBJECTIVE: The aim of this cross-sectional observational study was to investigate cytogenetic damage to the buccal mucosa in non-smokers and consumers of traditional combustible tobacco products and non-combustible alternatives.
METHODS: A total of 160 participants were divided into four groups according to the type of product used, including non-smokers, users of conventional combustible tobacco (cigarettes), heated tobacco, and electronic, tobacco-free vapor products (e-cigarettes). Buccal mucosa samples were analyzed using the micronucleus cytome assay to assess cytotoxic and genotoxic damage.
RESULTS: E-cigarette users showed significantly higher values for all tested parameters in the micronucleus test compared to non-smokers (p < 0.05). Similarly, users of tobacco heating products showed an increase in all parameters (p < 0.05), with the exception of the number of cells with micronuclei. Conventional cigarette smokers showed a notable increase in the number of binucleated cells and cells with karyorrhexis and karyolysis (p ≤ 0.05). When assessing the differences between users of traditional combustible tobacco products and non-combustible alternatives, these did not appear to be significant, except for e-cigarette users, who had significantly more cells with condensed chromatin (p ≤ 0.001), while users of tobacco heating products had more pyknotic cells (p ≤ 0.001).
CONCLUSIONS: The results of this study underscore the heightened occurrence of cytotoxic and genotoxic damage in users of both conventional combustible tobacco products and non-combustible alternatives compared to non-smokers, emphasizing the detrimental impact of these products on the oral mucosa.

UNASSIGNED: Periodontitis characterized by mild symptoms in the early stages, which makes diagnostics problematic. The gingival epithelium can be used for micronucleus assay since gums are the area affected by the disease.
UNASSIGNED: The aim of the study was to study the frequency of occurrence and the range of nuclear anomalies in gingival epithelium of healthy people and people with periodontitis.
UNASSIGNED: Scrapings of the gingival epithelium were made next to the central incisors (1.1) and molar teeth (1.7) in control and experimental groups (ten healthy males 35-50 years old and 10 males with periodontitis).
UNASSIGNED: The preparations were stained by Romanowsky-Giemsa. The frequency of nuclear aberrations (‰), the accumulation index, and the repair index were determined.
UNASSIGNED: The differences in the medians of nuclear aberrations were determined using Wilcoxon and the Van-der-Waerden tests. The pathology proportions were compared using the Z-test. To determine the predictors of periodontitis, receiver operator characteristic analysis was used. For multiple comparisons, the Bonferroni correction was used.
UNASSIGNED: In the experimental group, the range of nuclear aberrations was wider, the ratio of karyolysis in the unaffected area was higher, than that in control; perinuclear vacuoles were fewer and macronuclei were more in the affected area. The frequency of cells with micronuclei over 1.33‰ in the affected area is the periodontitis marker.
UNASSIGNED: Gingival epithelium can be used in micronucleus assay. Micronucleus test revealed a wider range of nuclear aberrations in the cells of the gingival epithelium and a higher frequency of occurrence of micronuclei in patients with periodontal disease compared to healthy subjects. Therefore, cytological signs of the inflammation appear earlier than the clinical ones and are verified more clearly. The markers of apoptosis and destruction of nuclei, and low repair index indicate normal elimination of damaged cells. An increased accumulation index in people with periodontitis may indicate the risk of malignant tumors.

According to the trade association PlasticEurope, global plastics production increased to 390.7 million tons in 2021. Unfortunately, the majority of produced plastics eventually end up as waste in the ocean or on land. Since synthetic plastics are not fully biodegradable, they tend to persist in natural environments and transform into micro- and nanoplastic particles due to fragmentation. The presence of nanoplastics in air, water, and food causes ecotoxicological issues and leads to human exposure. One of the main concerns is their genotoxic potential. Therefore, this study aimed to evaluate the internalization rates, cytotoxicity, and genotoxicity of polystyrene nanoparticles (PS-NPs) in human peripheral blood mononuclear cells (PBMCs) in vitro. The uptake of PS-NPs was confirmed with flow cytometry light scattering analysis. None of the tested nanoparticle concentrations had a cytotoxic effect on human PBMCs, as evaluated by a dual ethidium bromide/acridine orange staining technique. However, an alkaline comet assay results revealed a significant increase in the levels of primary DNA damage after 24 h of exposure to PS-NPs in a dose-dependent manner. Moreover, all tested PS-NPs concentrations induced a significant amount of micronucleated cells, as well. The results of this study revealed the genotoxic potential of commercially manufactured polystyrene nanoparticles and highlighted the need for more studies with naturally occurring plastic NPs.

This study investigates the genotoxicity and cytotoxicity of C17-sphinganine analog mycotoxin (C17-SAMT) using in vitro assays. C17-SAMT was previously identified as the cause of unusual toxicity in cultured mussels from the Bizerte Lagoon in northern Tunisia. While a previous in vivo genotoxicity study was inconclusive, in vitro results demonstrated that C17-SAMT induced an increase in micronucleus formation in human lymphoblastoid TK6 cells at concentrations of 0.87 µM and 1.74 µM. In addition, multiparametric cytotoxicity assays were performed in the human hepatoma HepaRG cell line, which showed that C17-SAMT induced mitochondrial dysfunction, decreased cellular ATP levels, and altered the expression of various proteins, including superoxide dismutase SOD2, heme oxygenase HO-1, and NF-κB. These results suggest that C17-SAMT is mutagenic in vitro and can induce mitochondrial dysfunction in HepaRG cells. However, the exact mode of action of this toxin requires further investigation. Overall, this study highlights the potential toxicity of C17-SAMT and the need for further research to better understand its effects.

The in vitro micronucleus (MN) assay is a component of most test batteries used in assessing potential genotoxicity. Our previous study adapted metabolically competent HepaRG cells to the high-throughput (HT) flow-cytometry-based MN assay for genotoxicity assessment (Guo et al. in J Toxicol Environ Health A 83:702-717, 2020b, https://doi.org/10.1080/15287394.2020.1822972 ). We also demonstrated that, compared to HepaRG cells grown as two-dimensional (2D) cultures, 3D HepaRG spheroids have increased metabolic capacity and improved sensitivity in detecting DNA damage induced by genotoxicants using the comet assay (Seo et al. in ALTEX 39:583-604, 2022, https://doi.org/10.14573/altex.22011212022 ). In the present study, we have compared the performance of the HT flow-cytometry-based MN assay in HepaRG spheroids and 2D HepaRG cells by testing 34 compounds, including 19 genotoxicants or carcinogens and 15 compounds that show different genotoxic responses in vitro and in vivo. 2D HepaRG cells and spheroids were exposed to the test compounds for 24 h, followed by an additional 3- or 6-day incubation with human epidermal growth factor to stimulate cell division. The results demonstrated that HepaRG spheroids showed generally higher sensitivity in detecting several indirect-acting genotoxicants (require metabolic activation) compared to 2D cultures, with 7,12-dimethylbenzanthracene and N-nitrosodimethylamine inducing higher % MN formation along with having significantly lower benchmark dose values for MN induction in 3D spheroids. These data suggest that 3D HepaRG spheroids can be adapted to the HT flow-cytometry-based MN assay for genotoxicity testing. Our findings also indicate that integration of the MN and comet assays improved the sensitivity for detecting genotoxicants that require metabolic activation. These results suggest that HepaRG spheroids may contribute to New Approach Methodologies for genotoxicity assessment.

UNASSIGNED: Although titanium-based implants are considered bioinert, it has been found that they are subject to corrosion and wear. This study aimed to evaluate the cytotoxic and genotoxic potential of two implant systems in gingival epithelial cells.
UNASSIGNED: Gingival swabs were taken three times from 91 subjects. The first swab was taken before dental implant placement, the second swab 90 days after dental implant placement and the third swab 21 days following the healing abutment placement. DNA damage was analyzed using the micronucleus test. Tested dental implants with corresponding healing abutments were Ankylos and Dentium SuperLine.
UNASSIGNED: Of all scored forms of cytogenetic damage in gingival cells of individuals after implementation of tested dental implant systems, only an increase in the number of binucleated cells (P ≤ 0.001) was significant in contrast to control values for both tested implant systems, 90 days after dental implant placement and 21 days following the healing abutment placement.
UNASSIGNED: It may be concluded that there are no titanium-based implant dependent cytogenetic damage in gingival epithelial cells. A slight increase in cytogenetic damage has been observed but it is of no biological relevance and might be associated with healing abutment induced effect.