A path from synthesis to emergency use authorization of molnupiravir as a COVID-19 therapy.

Coronaviruses are a group of enveloped viruses with non-segmented, single-stranded, and positive-sense RNA genomes. It belongs to the 'Coronaviridae family', responsible for various diseases, including the common cold, SARS, and MERS. The COVID-19 pandemic, which began in March 2020, has affected 209 countries, infected over a million people, and claimed over 50,000 lives. Significant efforts have been made by repurposing several approved drugs including antiviral, to combat the COVID-19 pandemic. Molnupiravir is found to be the first orally acting efficacious drug to treat COVID-19 cases. It was approved for medical use in the UK in November 2021 and other countries, including USFDA, which granted approval an emergency use authorization (EUA) for treating adults with mild to moderate COVID-19 patients. Considering the importance of molnupiravir, the present review deals with its various synthetic strategies, pharmacokinetics, bio-efficacy, toxicity, and safety profiles. The comprehensive information along with critical analysis will be very handy for a wide range of audience including medicinal chemists in the arena of antiviral drug discovery especially anti-viral drugs against any variant of COVID-19.

Genotoxic and antiproliferative properties of Endopleura uchi bark aqueous extract.

The bark extract from Endopleura uchi has been widely used in traditional medicine to treat gynecological-related disorders, diabetes, and dyslipidemias albeit without scientific proof. In addition, E. uchi bark extract safety, especially regarding mutagenic activities, is not known. The aim of this study was to determine the chemical composition, antitumor, and toxicological parameters attributed to an E. uchi bark aqueous extract. The phytochemical constitution was assessed by colorimetric and chromatographic analyzes. The antiproliferative effect was determined using sulforhodamine B (SRB) assay using 4 cancer cell lines. Cytotoxic and genotoxic activities were assessed utilizing MTT and comet assays, respectively, while mutagenicity was determined through micronucleus and Salmonella/microsome assays. The chromatographic analysis detected predominantly the presence of gallic acid and isoquercitrin. The antiproliferative effect was more pronounced in human colon adenocarcinoma (HT-29) and human breast cancer (MCF-7) cell lines. In the MTT assay, the extract presented an IC50 = 39.1 µg/ml and exhibited genotoxic (comet assay) and mutagenic (micronucleus test) activities at 20 and 40 µg/ml in mouse fibroblast cell line (L929) and mutagenicity in the TA102 and TA97a strains in the absence of S9 mix. Data demonstrated that E. uchi bark possesses bioactive compounds which exert cytotoxic and genotoxic effects that might be associated with its antitumor potential. Therefore, E. uchi bark aqueous extract consumption needs to be approached with caution in therapeutic applications.

Application of HepaRG cells for genotoxicity assessment: a review.

There has been growing interest in the use of human-derived metabolically competent cells for genotoxicity testing. The HepaRG cell line is considered one of the most promising cell models because it is TP53-proficient and retains many characteristics of primary human hepatocytes. In recent years, HepaRG cells, cultured in both a traditional two-dimensional (2D) format and as more advanced in-vivo-like 3D spheroids, have been employed in assays that measure different types of genetic toxicity endpoints, including DNA damage, mutations, and chromosomal damage. This review summarizes published studies that have used HepaRG cells for genotoxicity assessment, including cell model evaluation studies and risk assessment for various compounds. Both 2D and 3D HepaRG models can be adapted to several high-throughput genotoxicity assays, generating a large number of data points that facilitate quantitative benchmark concentration modeling. With further validation, HepaRG cells could serve as a unique, human-based new alternative methodology for in vitro genotoxicity testing.

Ecotoxicological evaluation of surface waters in Northern Namibia.

The increasing pressure on freshwater systems due to intensive anthropogenic use is a big challenge in central-northern Namibia and its catchment areas, the Kunene and the Kavango Rivers, and the Cuvelai-Etosha Basin, that provide water for more than 1 million people. So far, there is no comprehensive knowledge about the ecological status and only few knowledge about the water quality. Therefore, it is crucial to learn about the state of the ecosystem and the ecological effects of pollutants to ensure the safe use of these resources. The surface waters of the three systems were sampled, and three bioassays were applied on three trophic levels: algae, daphnia, and zebrafish embryos. Additionally, in vitro assays were performed to analyze mutagenicity (Ames fluctuation), dioxin-like potential (micro-EROD), and estrogenicity (YES) by mechanism-specific effects. The results show that acute toxicity to fish embryos and daphnia has mainly been detected at all sites in the three catchment areas. The systems differ significantly from each other, with the sites in the Iishana system showing the highest acute toxicity. At the cellular level, only weak effects were identified, although these were stronger in the Iishana system than in the two perennial systems. Algae growth was not inhibited, and no cytotoxic effects could be detected in any of the samples. Mutagenic effects and an estrogenic potential were detected at three sites in the Iishana system. These findings are critical in water resource management as the effects can adversely impact the health of aquatic ecosystems and the organisms within them.

Strategy proposal using QSAR models to approach mutagenicity assessment of non intentionally added substances in recycled plastic resins.

CONTEXT: Transition to the use of recycled plastics raises an issue concerning safety assessment of Non Intentionally Added Substances (NIAS). To assess the mutagenic potential of the recycled polyethylene impurities and to evaluate the need to perform in vitro assays on recycled resins, this study lies in identifying existing NIAS associated with recycled Low/High Density Polyethylene and assessing the mutagenicity data-gaps by employing in silico tools. METHODS: Quantitative Structure-Activity Relationship (QSAR) models predicting Ames mutagenicity were selected from literature, then NIAS were run to 1/evaluate performances of each model, 2/apply a QSAR strategy on the NIAS molecular space and address data-gaps. RESULTS: Among the 165 NIAS identified, experimental Ames results were not found for 50 substances while the substances with experimental data were predominantly negatives. No individual model was able to predict all NIAS due to applicability domain limitations. Taking into account 1/calculated performances, 2/availability of applicability domain, 3/description of the Training Set, an Integrated Strategy was founded including Sarpy, Consensus and Protox to extend the applicability domain. CONCLUSION & PERSPECTIVES: Existing data and predictions generated by this strategy suggest a low mutagenic potential of NIAS. Further investigation is needed to explore other genotoxicity mechanisms.

Anticancer Potential and Safety Profile of ß-Lapachone In Vitro.

Ipê is a plant of the Bignoniaceae family. Among the compounds extracted from this tree, lapachol is notable because its structural modification allows the production of ß-lapachone, which has anticancer properties. The objective of this work was to test this hypothesis at a cellular level in vitro and assess its potential safety for use. The following tests were performed: MTT cell viability assay, apoptotic index determination, comet assay, and micronucleus test. The results showed that ß-lapachone had a high cytotoxic capacity for all cell lines tested: ACP02 (gastric adenocarcinoma cells), MCF7 (breast carcinoma cells), HCT116 (colon cancer cells) and HEPG2 (hepatocellular carcinoma cells). Regarding genotoxicity, the exposure of cells to sublethal doses of ß-lapachone induced DNA damage (assessed by the comet assay) and nuclear abnormalities, such as nucleoplasmic bridges and nuclear buds (assessed by the micronucleus test). All tested cell lines responded similarly to ß-lapachone, except for ACP02 cells, which were relatively resistant to the cytotoxic effects of the compound in the MTT test. Our results collectively indicate that although ß-lapachone showed antiproliferative activity against cancer cell lines, it also caused harmful effects in these cells, suggesting that the use of ß-lapachone in treating cancer should be carried out with caution.

Urinary mutagenicity and bladder cancer risk in northern New England.

The etiology of bladder cancer among never smokers without occupational or environmental exposure to established urothelial carcinogens remains unclear. Urinary mutagenicity is an integrative measure that reflects recent exposure to genotoxic agents. Here, we investigated its potential association with bladder cancer in rural northern New England. We analyzed 156 bladder cancer cases and 247 cancer-free controls from a large population-based case-control study conducted in Maine, New Hampshire, and Vermont. Overnight urine samples were deconjugated enzymatically and the extracted organics were assessed for mutagenicity using the plate-incorporation Ames assay with the Salmonella frameshift strain YG1041 + S9. Logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) of bladder cancer in relation to having mutagenic versus nonmutagenic urine, adjusted for age, sex, and state, and stratified by smoking status (never, former, and current). We found evidence for an association between having mutagenic urine and increased bladder cancer risk among never smokers (OR = 3.8, 95% CI: 1.3-11.2) but not among former or current smokers. Risk could not be estimated among current smokers because nearly all cases and controls had mutagenic urine. Urinary mutagenicity among never-smoking controls could not be explained by recent exposure to established occupational and environmental mutagenic bladder carcinogens evaluated in our study. Our findings suggest that among never smokers, urinary mutagenicity potentially reflects genotoxic exposure profiles relevant to bladder carcinogenesis. Future studies are needed to replicate our findings and identify compounds and their sources that influence bladder cancer risk.

Synthetic auxin herbicide 2,4-D and its influence on a model BY-2 suspension.

2,4-D is a broadly used auxin herbicide. The presence of the 2,4-D synthetic auxin in the medium is imperative for long-term BY-2 tobacco suspension viability. The precise mechanism of this symbiosis of the suspension and the synthetic auxin remains unclear. Our goal was to study the hormonal regulation of the growth of the cell suspension; and to describe the experiments clarifying the interaction between the chosen growth regulators and phytohormones on the cellular level, specifically between the 2,4-D synthetic auxin and the native stress phytohormone - ethylene. This study examined the influence of low 2,4-D concentrations stimulating cell growth in vitro as well as the influence of high herbicide concentrations on the model tobacco BY-2 suspension. The culture took 6 days. Different parameters were evaluated, including the influence of different 2,4-D concentrations on the production of the phytohormone ethylene and its precursor 1-Aminocyclopropane-1-carboxylic acid (ACC) in the tobacco cells. The content of 2,4-D in the cells and the medium was established. The observations of the morphological changes showed that a heavy impregnation of the cell walls taking place depending on the concentration of 2,4-D. A dramatic increase in protective polysaccharides and a remodulation of the cell walls by the formation of a pectin shield in artificial conditions were expected and observed. At the same time, massive production of the stress phytohormone ethylene took place, and, because of that, plant mutagenicity, anomalous tumour-type proliferation growth, and the production of supercells were observed. The hypothesis of the protective shield is discussed.

Cytogenotoxicity and inflammatory response in liver of rats exposed to different doses of cannabis nano emulsions.

Cannabis is the most used illicit substance for recreational purposes around the world. However, it has become increasingly common to witness the use of approved cannabis preparations for symptoms management in various diseases. The aim of this study was to investigate the effects of cannabis nano emulsion in the liver of Wistar rats, with different proportions of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). For this, a total of 40 male Wistar rats were distributed into 5 groups, as follows (n = 8 per group): Control: G1, Experimental group (G2): treated with cannabis nano emulsion (THC and CBD) at a dose of 2.5 mg/kg, Experimental group (G3): treated with cannabis nano emulsion (THC and CBD) at a dose of 5 mg/kg, Experimental group (G4): treated with cannabis nano emulsion (CBD) at a dose of 2.5 mg/kg; Experimental group (G5): treated with cannabis nano emulsion (CBD) at a dose of 5 mg/kg. Exposure to the nano emulsion was carried out for 21 days, once a day, orally (gavage). Our results showed that cannabis nano emulsions at higher doses (5 mg/kg), regardless of the composition, induced histopathologic changes in the liver (G3 and G5) in comparison with the control group. In line with that, placental glutathione S-transferase (GST-P) positive foci increased in both G3 and G5 (p < 0.05), as well as the immune expression of Ki-67, vascular endothelial growth factor (VEGF) and p53 (p < 0.05). Also, the nano emulsion intake induced an increase in the number of micronucleated hepatocytes in G5 (p < 0.05) whereas G3 showed an increase in binucleated cells (p < 0.05). As for metanuclear alterations, karyolysis and pyknosis had an increased frequency in G3 (p < 0.05). Taken together, the results show that intake of cannabis nano emulsion may induce degenerative changes and genotoxicity in the liver in higher doses, demonstrating a clear dose-response relationship.

Preliminary study on the enhanced bioremediation of PAH-contaminated soil in Beijing and assessment of remediation effects based on toxicity tests.

In this study, we focused on soil contaminated by polycyclic aromatic hydrocarbons (PAHs) at typical coking-polluted sites in Beijing, conducted research on enhanced PAH bioremediation and methods to evaluate remediation effects based on toxicity testing, and examined changes in pollutant concentrations during ozone preoxidation coupled with biodegradation in test soil samples. The toxicity of mixed PAHs in soil was directly evaluated using the Ames test, and the correlation between mixed PAH mutagenicity and benzo(a)pyrene (BaP) toxicity was investigated in an effort to establish a carcinogenic risk assessment model based on biological toxicity tests to evaluate remediation effects on PAH-contaminated soil. This study provides a theoretical and methodological foundation for evaluating the effect of bioremediation on PAH-contaminated soil at industrially contaminated sites. The results revealed that the removal rate of PAHs after 5 min of O3 preoxidation and 4 weeks of soil reaction with saponin surfactants and medium was 83.22%. The soil PAH extract obtained after remediation had a positive effect on the TA98 strain at a dose of 2000 µg·dish-1, and the carcinogenic risk based on the Ames toxicity test was 8.98 times greater than that calculated by conventional carcinogenic PAH toxicity parameters. The total carcinogenic risk of the remediated soil samples was approximately one order of magnitude less than that of the original soil samples.

Are hydroxyapatite-based biomaterials free of genotoxicity? A systematic review.

Hydroxyapatite (HA) is a biomaterial widely used in clinical applications and pharmaceuticals. The literature on HA-based materials studies is focused on chemical characterization and biocompatibility. Generally, biocompatibility is analyzed through adhesion, proliferation, and differentiation assays. Fewer studies are looking for genotoxic events. Thus, although HA-based biomaterials are widely used as biomedical devices, there is a lack of literature regarding their genotoxicity. This systematic review was carried out following the PRISMA statement. Specific search strategies were developed and performed in four electronic databases (PubMed, Science Direct, Scopus, and Web of Science). The search used "Hydroxyapatite OR Calcium Hydroxyapatite OR durapatite AND genotoxicity OR genotoxic OR DNA damage" and "Hydroxyapatite OR Calcium Hydroxyapatite OR durapatite AND mutagenicity OR mutagenic OR DNA damage" as keywords and articles published from 2000 to 2022, after removing duplicate studies and apply include and exclusion criteria, 53 articles were identified and submitted to a qualitative descriptive analysis. Most of the assays were in vitro and most of the studies did not show genotoxicity. In fact, a protective effect was observed for hydroxyapatites. Only 20 out of 71 tests performed were positive for genotoxicity. However, no point mutation-related mutagenicity was observed. As the genotoxicity of HA-based biomaterials observed was correlated with its nanostructured forms as needles or rods, it is important to follow their effect in chronic exposure to guarantee safe usage in humans.

Lack of in vivo mutagenicity of carbendazim in the liver and glandular stomach of MutaMice.

BACKGROUND: Carbendazim (methyl 2-benzimidazolecarbamate, CASRN: 10605-21-7) exhibits spindle poisoning effects and is widely used as a fungicide. With respect to genotoxicity, carbendazim is deemed to be non-mutagenic in vitro, but it causes indicative DNA damage in vivo and chromosome aberrations in vitro and in vivo. In this study, we examined the mutagenicity of carbendazim in vivo. RESULTS: MutaMice were treated with carbendazim orally at doses of 0 (corn oil), 250, 500, and 1,000 mg/kg/day once a day for 28 days. A lacZ assay was used to determine the mutant frequency (MF) in the liver and glandular stomach of mice. MutaMice were administered up to the maximum dose recommended by the Organization for Economic Co-operation and Development Test Guidelines for Chemicals No. 488 (OECD TG488). The lacZ MFs in the liver and glandular stomach of carbendazim-treated animals were not significantly different from those in the negative control animals. In contrast, positive control animals exhibited a significant increase in MFs in both the liver and glandular stomach. CONCLUSIONS: Carbendazim is non-mutagenic in the liver and glandular stomach of MutaMice following oral treatment.

Antimutagenic activity of different forms of Bifidobacterium lactis probiotic against aflatoxin B1 by Ames method.

The health risks caused by aflatoxins, as one of the most important contaminants of human food and feed and the main cause of cancer, especially hepatocellular carcinoma (HCC) were investigated. The aim of the study was to assess the antimutagenic effects of Bifidobacterium lactis (B. lactis) probiotic against aflatoxin B1 (AFB1). The study was conducted with 27 treatments and three replications. The independent variables were aflatoxin concentrations at three levels of 5, 15, and 25 ng/g and probiotic content in three forms of cellular sedimentation (CS), cell-free supernatant (CFS), and cell suspension. The antimutagenic activity of B. lactis against AFB1 was measured. The lowest score of antimutagenic activity of B. lactis was observed in bacterial cellular sediment treatment at 107 CFU/g and 25 ng/g of AFB1 (20.8 ± 3.80%) and the highest score was achieved with cell suspension at 109 CFU/g and 5 ng/g of AFB1 (74.9 ± 7.11%). In addition, the lack of mutagenicity of probiotics was confirmed. Therefore, probiotics not only alleviate aflatoxin in food matrices and benefit the consumer, but also notably decrease mutagenicity of AFB1.

Mutagenicity assessment of two potential impurities in preparations of 5-amino-2,4,6 triiodoisophthalic acid, a key intermediate in the synthesis of the iodinated contrast agent iopamidol.

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). However, contrary to the in silico prediction, neither chemical was mutagenic in the Ames test (plate incorporation method) with or without S9 metabolic activation.

Assessment of the performance of the Ames MPF™ assay: A multicenter collaborative study with six coded chemicals.

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. The data generated by the participating laboratories was in excellent agreement (93%), and the similarity of their dose response curves, as analyzed with sophisticated statistical approaches further confirmed the suitability of the Ames MPF™ assay as an alternative to the Ames test on agar plates, but with advantages with respect to significantly reduced amount of test substance and S9 requirements, speed, hands-on time and, potentially automation.

Organic toxicants and emerging contaminants in hospital interiors before and during the SARS-CoV2 pandemic: alkanes and PAHs.

Indoor pollution and deposition dust (DD), in particular, are acquiring concern, due to long exposure time and importance of intake by humans through contact and ingestion. Hospitals look a special category of sites, owing to peculiar contaminants affecting them and to presence of people prone to adverse effects induced by toxicants. Four in-field campaigns aimed at understanding the chemical composition of DD were performed in five Italian hospitals. Measurements were performed before (autumn 2019), during (spring 2021), and after (winter 2022) the peak of SARS-CoV2 and when restrictions caused by pandemic were revoked (winter 2023). Parallel measurements were made outdoors (2022), as well as in a university and a dwelling. Targeted contaminants were n-alkanes and polycyclic aromatic hydrocarbons (PAHs), while iso- and anteiso-alkanes were analyzed to assess the impact of tobacco smoking. Total n-alkanes ranged from 3.9 ± 2.3 to 20.5 ± 4.2 mg/g, with higher percentages of short chain homologs in 2019. PAHs ranged from 0.24 ± 0.22 to 0.83 ± 0.50 mg/g, with light congeners (≤ 228 a.m.u.) always exceeding the heavy ones (≥ 252 a.m.u.). According to carbon preference indexes, alkanes originated overall from anthropogenic sources. Microorganisms resulted to affect a hospital, and tobacco smoke accounted for ~ 4-20‰ of DD mass. As for PAH sources, the diagnostic concentration ratios suggested the concourse of biological matter burning and vehicle emission. Benzo[a]pyrene equivalent carcinogenic and mutagenic potencies of depositions at hospitals ranged ~ 9-39 µg/g and ~ 15-76 µg/g, respectively, which seems of concern for health. DD composition in hospitals was different from that outside the premises, as well as that found at university and at dwelling.

Prediction of molecular-specific mutagenic alerts and related mechanisms of chemicals by a convolutional neural network (CNN) model based on SMILES split.

Structural alerts (SAs) are essential to identify chemicals for toxicity evaluation and health risk assessment. We constructed a novel SMILES split-based deep learning model (SSDL) that was trained and verified with 5850 chemicals from the ISSSTY database and 384 external test chemicals from published papers. The training accuracy was above 0.90 and the evaluation metrics (precision, recall and F1-score) all reached 0.78 or above on both internal and external test chemicals. In this model, the molecular-specific fragment importance of chemicals was first quantified independently. Then, the SA identification method based on the importance of these fragments was statistically analyzed and verified with the ISSSTY test and external test chemicals containing one of 28 typical SAs, and most of the performances were better than that of expert rules. Furthermore, a mutagenicity mechanism prediction method was developed using 237 chemicals with four known mutagenic mechanisms based on molecular similarity calibrated by the SSDL method and fragment importance, which significantly improved accuracy in three mechanisms and had comparable accuracy in the other one compared to traditional methods. Overall, the SSDL model quantifying fragment toxicity within molecules would be a novel potentially powerful tool in the determination and visualization of molecular-specific SAs and the prediction of mutagenicity mechanisms for environmental or industrial compounds and drugs.

Mutagenicity Assessment of Homologous Series of Methyl Ester Sulphonates (MES) Using the Bacterial Reverse Mutation (Ames) Test.

Methyl ester sulphonate (MES) is an anionic surfactant that is suitable to be used as an active ingredient in household products. Four palm-based MES compounds with various carbon chains, namely C12, C14, C16 and C16/18 MES, were assayed by the in vitro bacterial reverse mutation (Ames) test in the Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 and the Escherichia coli strain WP2 uvrA, with the aim of establishing the safety data of the compounds, specifically their mutagenicity. The test was also carried out on linear alkylbenzene sulphonate (LAS) for comparison. The plate incorporation method was conducted according to the Organization for Economic Cooperation and Development (OECD) Test Guideline 471. All compounds were tested at five analysable non-cytotoxic concentrations, varying from .001 mg/plate to 5 mg/plate, with and without S-9 metabolic activation. All tested concentrations showed no significant increase in the number of revertant colonies compared to revertant colonies of the negative control. The Ames test indicated that each concentration of C12, C14, C16, C16/18 MES, and LAS used in this study induced neither base-pair substitutions nor frame-shift mutations in the S. typhimurium strains TA98, TA100, TA1535, and TA1537 and the E. coli strain WP2 uvrA. The results showed that C12, C14, C16 and C16/18 MES have no potential mutagenic properties in the presence and absence of S-9 metabolic activation, similarly to LAS. Therefore, the MES is safe to be used as an alternative to petroleum-based surfactants for household cleaning products.

Matrine and Oxymatrine: evaluating the gene mutation potential using in silico tools and the bacterial reverse mutation assay (Ames test).

The quinolizidine alkaloids matrine and its N-oxide oxymatrine occur in plants of the genus Sophora. Recently, matrine was sporadically detected in liquorice products. Morphological similarity of the liquorice plant Glycyrrhiza glabra with Sophora species and resulting confusion during harvesting may explain this contamination, but use of matrine as pesticide has also been reported. The detection of matrine in liquorice products raised concern as some studies suggested a genotoxic activity of matrine and oxymatrine. However, these studies are fraught with uncertainties, putting the reliability and robustness into question. Another issue was that Sophora root extracts were usually tested instead of pure matrine and oxymatrine. The aim of this work was therefore to determine whether matrine and oxymatrine have potential for causing gene mutations. In a first step and to support a weight-of-evidence analysis, in silico predictions were performed to improve the database using expert and statistical systems by VEGA, Leadscope (Instem®), and Nexus (Lhasa Limited). Unfortunately, the confidence levels of the predictions were insufficient to either identify or exclude a mutagenic potential. Thus, in order to obtain reliable results, the bacterial reverse mutation assay (Ames test) was carried out in accordance with OECD Test Guideline 471. The test set included the plate incorporation and the preincubation assay. It was performed with five different bacterial strains in the presence or absence of metabolic activation. Neither matrine nor oxymatrine induced a significant increase in the number of revertants under any of the selected experimental conditions. Overall, it can be concluded that matrine and oxymatrine are unlikely to have a gene mutation potential. Any positive findings with Sophora extracts in the Ames test may be related to other components. Notably, the results also indicated a need to extend the application domain of respective (Q)SAR tools to secondary plant metabolites.

Mutagenicity assessment of high-power 1.6-THz pulse laser radiation.

The effect of terahertz (THz) radiation has been studied in medicine. However, there is a lack of scientific information regarding its possible mutagenicity. Therefore, the present study aimed to assess the mutagenicity of 1.6 THz laser irradiation. The Ames test was conducted using five bacterial tester strains. The bacteria were subjected to (i) 1.6 THz laser irradiation at 3.8 mW/cm2 for 60 min using a tabletop THz pulse laser system, (ii) ultraviolet irradiation, (iii) treatment with positive control chemicals (positive control) or (iv) treatment with the solvent used in the positive control (negative control). After treatment, the bacterial suspensions were cultured on minimal glucose agar to determine the number of revertant colonies. In addition, the comet assay was performed using fibroblasts (V79) to assess possible DNA damage caused by the THz laser irradiation. The Ames test demonstrated that the THz laser irradiation did not increase the number of revertant colonies compared to that in the negative control group, whereas the ultraviolet irradiation and positive control treatment increased the number of revertant colonies. Thus, 1.6 THz laser irradiation is unlikely to be mutagenic. The comet assay additionally suggests that the THz laser irradiation unlikely induce cellular DNA damage.