Mutagenic Effects Research Articles

IMPACT OF HAZARDOUS TOXIC FACTORS OF FIRES DURING MILITARY ACTIONS ON ECOSYSTEMS AND POPULATION LIFE ACTIVITIES

It has been analysed that wildfires are the most influential factor in environmental pollution. The ecological consequences of wildfires consist primarily of atmospheric air pollution with carbon monoxide, products of combustion of combustible materials, and the burning of oxygen. Plant combustion also contributes significantly to planetary environmental changes: climate warming, ozone depletion, acid rain, chemical and radioactive pollution of the atmosphere, water, and soil. With wildfires, soot particles, that is, carbon and products of incomplete combustion of wood, enter the air. Smoke, which is formed during fires, explosions, ignitions, etc., during the combustion of plant biomass (grasses, leaves from trees and shrubs, mosses, lichens, peatlands, forest litter and needles), is an aerosol-gas mixture containing hazardous substances dangerous to the environment and humans. Biomass burning is a global source of gas and dust pollution of the atmosphere and is considered one of the determining factors of ecotoxicological risks for public health. The negative impact of fires from military actions on the human body is acute and delayed. Acute exposure leads to hypoxia due to carbon oxides, increased consumption of oxygen from the air during combustion, irritation of the respiratory tract, and difficulty breathing. Delayed exposure is due to toxic, mutagenic, and carcinogenic effects. The toxic impact of fires on the life and health of the population is not only a threat to life but also an adverse effect on human organisms of heavy compounds of chemical substances represented by the combustion products of plant biomass of forests, peatlands, vast agricultural lands, including crop rotations and pastures. Often, this impact occurs in combination with typical atmospheric air pollution: emissions from industrial enterprises and motor vehicles. The peculiarity of such a combination is the complex synergistic effects of chemical compounds and high air temperature with significant relative duration (decades, months) of emergency environmental situations. Keywords: toxic factors, fires, ecosystem, human activity.

New insights into the typical nitrogen-containing heterocyclic compound-quinoline degradation and detoxification by microbial consortium: Integrated pathways, meta-transcriptomic analysis and toxicological evaluation

As the primary source of COD in industrial wastewater, quinoline has aroused increasing attention because of its potential teratogenic, carcinogenic, and mutagenic effects in the environment. The activated sludge isolate quinoline-degrading microbial consortium (QDMC) efficiently metabolizes quinoline. However, the molecular underpinnings of the degradation mechanism of quinoline by QDMC have not been elucidated. High-throughput sequencing revealed that the dominant genera included Diaphorobacter, Bacteroidia, Moheibacter and Comamonas. Furthermore, a positive strong correlation was observed between the key bacterial communities (Diaphorobact and Bacteroidia) and quinoline degradation. According to metatranscriptomics, genes associated with quorum sensing, ABC transporters, component systems, carbohydrate, aromatic compound degradation, energy metabolism and amino metabolism showed high expression, thus improving adaptability of microbial community to quinoline stress. In addition, the mechanism of QDMC in adapting and resisting to extreme environmental conditions in line with the corresponding internal functional properties and promoting biogegradation efficiency was illustrated. Based on the identified products, QDMC effectively mineralized quinoline into low-toxicity metabolites through three major metabolic pathways, including hydroxyquinoline, 1,2,3,4-H-quinoline, 5,6,7,8-tetrahydroquinoline and 1-oxoquinoline pathways. Finally, toxicological, genotoxicity and phytotoxicity studies supported the detoxification of quinoline by the QDMC. This study provided a promising approach for the stable, environmental-friendly and efficient bioremediation applications for quinoline-containing wastewater.

Mutagenic effect of ultraviolet rays on sex expression in summer squash genotypes

The present study aimed to induce genetic variations within the control of sex expression in summer squash using ultraviolet rays (UV) as a physical source of mutations in plants. Because the sex expression in summer squash is fundamentally controlled mainly by genetics and partially by the environment. Therefore, this study tries to increase floral differentiation of female flowers, as well as decrease male flowers developed per plant, because summer squash usually exhibit more male flowers and lower female flowers. This will cause decreases in fruits yield per plant. This study was designed in a randomized complete block design with a factorial investigation. It was included four genotypes of summer squash subjected to four exposure periods of UV rays, with three repetitions for each experimental unit. The results showed that genotype number four increased the features of female flowers by 28% and 14% at 4 and 8 minutes of exposure period, respectively. The 12 – minute exposure period significantly increased floral differentiation among all genotypes toward male flowers developed per plant. Meanwhile, genotype number two enhanced floral differentiation toward female flowers by 14% at 8 minutes of exposure period, indicating that these few periods of exposure to UV irradiation may be responsible for induced benefit mutations in cucurbits affected on sex expression, as it induced high number of female flowers. The results indicated that UV irradiation had a direct role in promoting floral differentiation as it inducement higher female flowers in some genotypes leading to improve floral characteristics, as a consequence increased fruits yield per plant.

Unlocking the potential of aromatase inhibitors: recent advances in drug design, synthesis, docking activity, and in vitro bioactivity evaluations

Breast cancer, a global health concern claiming approximately 685,000 lives in 2020, necessitates continual advancements in therapeutic strategies. Estrogen and aromatase play pivotal roles in hormone-responsive breast cancer, with 80% of patients exhibiting estrogen receptor-positive tumors. Aromatase inhibitors (AIs), notably non-steroidal inhibitors like anastrozole and letrozole, have significantly improved outcomes, yet challenges persist, including side effects. This review focuses on recent developments in AIs, exploring xanthone derivatives, imidazole derivatives, and curcumin derivatives as potential inhibitors of aromatase. Molecular docking studies, employing Auto Dock and other tools, reveal the binding affinities and interactions of these compounds with the aromatase enzyme. Among xanthones, Erythrommone emerges as a potent inhibitor, holding promise for clinical trials. Imidazole derivatives, synthesized through the Debus-Radziszewski reaction, demonstrate anticancer potential, with compounds like 1a exhibiting superior efficacy against MCF7 cells. ADME-Tox analyses indicate promising drug-likeness but reveal potential mutagenic effects and environmental impacts. Curcumin derivatives, particularly 1,5-diaryl-1,4-pentadien-3-ones, present alternatives to address curcumin's bioavailability challenges. A study of 25 compounds (DKC) identifies DKC-10 as a potent inhibitor, outperforming established breast cancer drugs in terms of binding affinity and interactions with aromatase and ERα+ receptors. These findings underscore the importance of exploring diverse chemical structures in developing AIs, paving the way for more effective and well-tolerated therapeutics. The integration of computational techniques, such as molecular docking studies, accelerates drug discovery by predicting interactions at the molecular level. Overall, this comprehensive review provides valuable insights into the evolving landscape of aromatase inhibitors, offering a roadmap for future research and the development of advanced breast cancer therapeutics.

Genotoxic and Mutagenic Assessment of PT-31, a Molecule with Antipsychotic Potential

Abstract: The PT-31 molecule, a potential antipsychotic, has demonstrated promising results when orally administrated to in vivo models. A recent study suggested the genotoxic and mutagenic po-tential of PT-31 after acute treatment by intraperitoneal route. This study aimed to evaluate PT-31 potential of inducing genotoxic or mutagenic damage after acute oral administration. For that, adult males and females Balb/C mice were treated acutely by oral administration with vehicle or PT-31 in three different doses (10, 20, and 40 mg kg-1). After 24 hours from PT-31 administration, animals were euthanized for performing the comet and micronucleus assays. None of the tested groups of PT-31 presented a significant increase in damage index and MN frequency. However, they presen-ted the following tendency on damage index: females presented a tendency at 40 mg kg-1 and males at 20 mg kg-1. Regarding the MN assay, male mice at the highest dose of 40 mg kg-1 presented a tendency of increased MN frequency. Also, there was a significant increase in PCE/NCE ratio in male mice. Results suggest that the male mice group presented higher susceptibility to damage. The tendency of increased damage to DNA and MN frequency suggests that the molecule PT-31 may induce reparable damage to DNA, and these DNA strand repairs may have originated from the MN. However, significant genotoxic and mutagenic effects were not observed. This study reinforces the atypical profile of the molecule as much as its safety by oral route administration.

A mutation rate model at the basepair resolution identifies the mutagenic effect of polymerase III transcription.

De novo mutations occur at substantially different rates depending on genomic location, sequence context and DNA strand. The success of methods to estimate selection intensity, infer demographic history and map rare disease genes, depends strongly on assumptions about the local mutation rate. Here we present Roulette, a genome-wide mutation rate model at basepair resolution that incorporates known determinants of local mutation rate. Roulette is shown to be more accurate than existing models. We use Roulette to refine the estimates of population growth within Europe by incorporating the full range of human mutation rates. The analysis of significant deviations from the model predictions revealed a tenfold increase in mutation rate in nearly all genes transcribed by polymerase III (Pol III), suggesting a new mutagenic mechanism. We also detected an elevated mutation rate within transcription factor binding sites restricted to sites actively used in testis and residing in promoters.

Polycyclic aromatic hydrocarbons in the sediments of highly polluted coastal area in the Red Sea: levels, spatial distribution, and risk assessment.

The southern part of the Jeddah coast faces a range of pollution challenges that can impact the water quality and ecosystem in the area. Pollution sources are represented mainly by treated wastewater (TWW), harbor activities, and atmospheric deposition from vehicle exhaustemissions. Polycyclic aromatic hydrocarbons (PAHs) are among the persistent organic pollutants that interfere with all environmental matrices and could cause humane mutagenic and carcinogenic effects. In the present study, 16 priority parent and 21 methylated PAHs (∑37PAHs) were assessed in the sediments of three hot spot coastal sites (Islamic Jeddah port, Al-Arbaeen, and Al-Shabab lagoons) to evaluate the factors affecting their spatial distribution, examine their probable sources and potential adverse effects. The total detected concentrations of ∑37PAHs ranged from 785.9 to 8359.8ng/g dw (average: 2296.3 ± 2017.3ng/g dw). The highest levels of ∑37PAHs were detected near TWW stations. The highest individual PAH congeners observed were phenanthrene, anthracene, and pyrene. PAH molecular diagnostic ratios pointed out different pyrogenic sources. In some specific stations, there was an overlap of petrogenic origin. The sediment samples contained high concentrations of methylated PAHs, with concentrations ranging from 558.42 to 6321.21ng/g dw and an average concentration of 1679.1 ± 1430.7ng/g dw. The sediment quality guidelines indicated that adverse biological effects are likely to occur at least at the two TWW disposal stations and the sediments in these stations are at risk. The values of the mutagenic equivalence quotient (MEQ) and toxic equivalence quotient (TEQ) of carcinogenic PAHs were recorded at 39.88 and 33.17ng/g, respectively.

Determination of biochemical and histopathological changes on testicular and epididymis tissues induced by exposure to insecticide Imidacloprid during postnatal development in rats

BackgroundImidacloprid is a neonicotinoid insecticide belonging to the chloronicotinyl nitroguanidine chemical family. Toxicity of IMD for mammals in scientific studies has shown high mutagenic, immunotoxic, teratogenic and neurotoxic effects. The present study was designed to assess the toxic effects of imidacloprid (IMD) on the testicular and epididymis tissues as well as testosterone levels of neonatal male rats.MethodsNeonatal male rats from postnatal day (PND) 1 to PND 26 were consecutively administered with different concentrations of IMD (1, 5 and 10 mg/kg) subcutaneously. The effect of IMD on body and organ weight, lipid profile, histopathological alterations, oxidative stress and altered testosterone levels were assessed in the testis and plasma.ResultsThe results of body weight gain showed a significant difference in group 4 (10 mg/kg) animals as compared to the control. A significant increase in total cholesterol and triglycerides, while a decrease in high-density lipoprotein concentrations was evident. Similarly, a significant decrease in concentrations of antioxidant enzymes (CAT and SOD) among all the IMD-treated groups was evident, when compared to the control. Increased production of ROS was also noticed in the highest-dose treatment group. Further, we observed that IMD-treated rats indicated histopathological changes in the testis and epididymis along with a significant decrease in the plasma testosterone concentrations among IMI-treated groups in contrast to the control. Histological examination of the testis of IMD-treated neonatal male rats also showed decreased spermatogenesis in the treated groups when compared to the control. Furthermore, an increase in lumen diameter and a decrease in epithelial height of seminiferous tubules were also observed in IMD-treated rats in comparison with the control.ConclusionIt is concluded that sub-chronic exposure to IMD in neonatal male rats may induce histopathological changes in reproductive tissues and damage normal testicular functions via inducing oxidative stress, decrease in body weight, disturbing normal blood lipid profile and testosterone concentration. IMD exposure can induce pathophysiological effects calls for further evaluation of this widely used insecticide.

Glyoxal acid-free (GAF) histological fixative is a suitable alternative to formalin: results from an open-label comparative non-inferiority study

Formalin, an aqueous solution of formaldehyde, has been the gold standard for fixation of histological samples for over a century. Despite its considerable advantages, growing evidence points to objective toxicity, particularly highlighting its carcinogenicity and mutagenic effects. In 2016, the European Union proposed a ban, but a temporary permission was granted in consideration of its fundamental role in the medical-diagnostic field. In the present study, we tested an innovative fixative, glyoxal acid-free (GAF) (a glyoxal solution deprived of acids), which allows optimal tissue fixation at structural and molecular level combined with the absence of toxicity and carcinogenic activity. An open-label, non-inferiority, multicentric trial was performed comparing fixation of histological specimens with GAF fixative vs standard phosphate-buffered formalin (PBF), evaluating the morphological preservation and the diagnostic value with four binary score questions answered by both the central pathology reviewer and local center reviewers. The mean of total score in the GAF vs PBF fixative groups was 3.7 ± 0.5 vs 3.9 ± 0.3 for the central reviewer and 3.8 ± 0.5 vs 4.0 ± 0.1 for the local pathologist reviewers, respectively. In terms of median value, similar results were observed between the two fixative groups, with a median value of 4.0. Data collected indicate the non-inferiority of GAF as compared to PBF for all organs tested. The present clinical performance study, performed following the international standard for performance evaluation of in vitro diagnostic medical devices, highlights the capability of GAF to ensure both structural preservation and diagnostic value of the preparations.

Genotoxic and Mutagenic Effects of the Alternaria Mycotoxin Alternariol in Combination with the Process Contaminant Acrylamide.

Humans are constantly exposed to mixtures of different xenobiotics through their diet. One emerging concern is the Alternaria mycotoxin alternariol (AOH), which can occur in foods typically contaminated by the process contaminant acrylamide (AA). AA is a byproduct of the Maillard reaction produced in carbohydrate-rich foods during thermal processing. Given the genotoxic properties of AOH and AA as single compounds, as well as their potential co-occurrence in food, this study aimed to assess the cytotoxic, genotoxic, and mutagenic effects of these compounds in combination. Genotoxicity was assessed in HepG2 cells by quantifying the phosphorylation of the histone γ-H2AX, induced as a response to DNA double-strand breaks (DSBs). Mutagenicity was tested in Salmonella typhimurium strains TA98 and TA100 by applying the Ames microplate format test. Our results showed the ability of AOH and AA to induce DSBs and increase revertant numbers in S. typhimurium TA100, with AOH being more potent than AA. However, no synergistic effects were observed during the combined treatments. Notably, the results of the study suggest that the compounds exert mutagenic effects primarily through base pair substitutions. In summary, the data indicate no immediate cause for concern regarding synergistic health risks associated with the consumption of foods co-contaminated with AOH and AA.

Toxicological assessment of minoxidil: A drug with therapeutic potential besides alopecia

Minoxidil is regularly prescribed for alopecia, and its therapeutic potential has expanded in recent times. However, few studies have been conducted to evaluate its toxicity, and controversial findings regarding its mutagenic activities remain unsolved. This study aimed to access cytotoxic, genotoxic, and mutagenic properties of minoxidil using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, comet assay, and micronucleus test in mouse fibroblast (L929) cells and its point mutation induction potential in the Salmonella/microsome assay. Furthermore, an in vivo toxicity assessment was conducted in Caenorhabditis elegans. Minoxidil showed cytotoxicity at 2.0 mg/mL in MTT assay. Genotoxicity was observed after 3 h treatment in L929 cells using comet assay. No mutagenic effect was observed in both the micronucleus test and the Salmonella/microsome assay. The lethal dose 50 in C. elegans was determined to be 1.75 mg/mL, and a delay in body development was detected at all concentrations. In conclusion, minoxidil induces DNA damage only in early treatment, implying that this DNA damage may be repairable. This observation corroborates the absence of mutagenic activities observed in L929 cells and Salmonella typhimurium strains. However, the toxicity of minoxidil was evident in both C. elegans and L929 cells, underscoring the need for caution in its use.

Secreted cyclophilin A is non-genotoxic but acts as a tumor promoter

Chronic inflammation is associated with malignant transformation and creates the microenvironment for tumor progression. Cyclophilin A (CypA) is one of the major pro-inflammatory mediators that accumulates and persists in the site of inflammation in high doses over time. According to multiomics analyses of transformed cells, CypA is widely recognized as a pro-oncogenic factor. Vast experimental data define the functions of intracellular CypA in carcinogenesis, but findings on the role of its secreted form in tumor formation and progression are scarce. In the studies here, we exploit short-term in vitro and in vivo tests to directly evaluate the mutagenic, recombinogenic, and blastomogenic effects, as well as the promoter activity of recombinant human CypA (rhCypA), an analogue of secreted CypA. Our findings showed that rhCypA had no genotoxicity and, thus, was neither involved in nor influenced the initiation stage of carcinogenesis. At high doses, rhCypA could disrupt gap junctions in rat liver epithelial IAR-2 cells in vitro by decreasing the expression of connexins 26 and 43 in these cells and inhibit A549 cell adhesion. These data suggested that rhCypA could contribute to epithelial-mesenchymal transition in malignant cells. The research presented here elucidated the role of secreted CypA in carcinogenesis, revealing that it is not a tumor initiator but can act as a tumor promoter at high concentrations.

Mebudipine as an Overlooked Cardioprotective Drug: A Review Study

Context: Calcium channel blockers (CCBs) play a crucial role in the treatment of cardiovascular diseases. Mebudipine, a dihydropyridine derivative CCB, was first synthesized in 1997. This study explores the potential benefits of mebudipine in managing cardiovascular disease, particularly as a derivative of nifedipine. Evidence Acquisition: The article succinctly presents the advancements in mebudipine research, which were uncovered through extensive searches in reputable scientific databases such as ScienceDirect, Google Scholar, Scopus, and PubMed, conducted by 2 blinded researchers. The search focused on studies relevant to mebudipine, using specific keywords. Results: Mebudipine exhibits cardioprotective effects, reducing the occurrence of arrhythmias and minimizing heart tissue damage. Additionally, it has been found to enhance the levels of nitric oxide metabolites. Due to its limited solubility in water, mebudipine is typically administered using a nanoemulsion. Importantly, it has been deemed a safe drug without mutagenic effects. Conclusions: Our review study underscores that mebudipine not only has a cardioprotective effect but also offers protection to other organs against various forms of injury induction. The mechanisms responsible for these protective effects may be linked to its ability to counteract oxidative stress, prevent apoptosis, and mitigate inflammation. Nevertheless, further research is needed to fully elucidate its potential.

Genome instability footprint under rapamycin and hydroxyurea treatments.

The mutational processes dictating the accumulation of mutations in genomes are shaped by genetic background, environment and their interactions. Accurate quantification of mutation rates and spectra under drugs has important implications in disease treatment. Here, we used whole-genome sequencing and time-resolved growth phenotyping of yeast mutation accumulation lines to give a detailed view of the mutagenic effects of rapamycin and hydroxyurea on the genome and cell growth. Mutation rates depended on the genetic backgrounds but were only marginally affected by rapamycin. As a remarkable exception, rapamycin treatment was associated with frequent chromosome XII amplifications, which compensated for rapamycin induced rDNA repeat contraction on this chromosome and served to maintain rDNA content homeostasis and fitness. In hydroxyurea, a wide range of mutation rates were elevated regardless of the genetic backgrounds, with a particularly high occurrence of aneuploidy that associated with dramatic fitness loss. Hydroxyurea also induced a high T-to-G and low C-to-A transversion rate that reversed the common G/C-to-A/T bias in yeast and gave rise to a broad range of structural variants, including mtDNA deletions. The hydroxyurea mutation footprint was consistent with the activation of error-prone DNA polymerase activities and non-homologues end joining repair pathways. Taken together, our study provides an in-depth view of mutation rates and signatures in rapamycin and hydroxyurea and their impact on cell fitness, which brings insights for assessing their chronic effects on genome integrity.

Safety Assessment of Recycled Plastics from Post-Consumer Waste with a Combination of a Miniaturized Ames Test and Chromatographic Analysis

European circular economy goals require the use of recycled polymers in sensitive applications such as food packaging. As plastic recyclates can contain unknown post-consumer substances, the European Food Safety Authority evaluates recycling processes using a worst-case assumption: all contaminants are DNA-reactive mutagens/carcinogens with extremely low safety thresholds. The current data are insufficient to estimate whether this assumption is justified. To provide scientific evidence on the presence of DNA-reactive mutagens in recycled plastics, 119 input and output samples from plastic recycling were tested with a miniaturized Ames test. DNA-reactive mutagens were not detected in recycled polyethylene terephthalate, which is already approved for food contact. However, other types of recycled plastics (polyethylene, polypropylene and polystyrene), which are currently unauthorized for food contact, showed DNA-reactive, mutagenic effects in a total of 51 samples. The DNA-reactive substances that are responsible for the detected mutagenic activity could not be identified by comparison of the bioassay data with analytical results from a chromatographical screening. The data from the Ames test analysis of different independent batches and a comparison of input and output material indicate that the DNA-reactive contaminants are not randomly introduced through the misuse of recycled packaging by consumers, but are systematically formed during the recycling process from precursors in the input. This publication highlights the need to identify the source for this critical contaminant to enable the future use of polyethylene, polypropylene and polystyrene in sensitive applications.

Toxic, genotoxic, mutagenic, and bioaccumulative effects of metal mixture from settleable particulate matter on American bullfrog tadpoles (Lithobates catesbeianus)

Amphibians are more susceptible to environmental stressors than other vertebrates due to their semipermeable skin and physiological adaptations to living in very specific microhabitats. Therefore, the aim of the present study was to investigate the effects of a metal mixture from settleable particulate matter (SePM) released from metallurgical industries on Lithobates catesbeianus tadpoles. Endpoints analyzed included metal bioconcentration, morphological (biometrical indices), hematological parameters (hemoglobin and blood cell count), and erythrocyte DNA damage (genotoxicity and mutagenicity). American bullfrog tadpoles (Gosner's stage 25) were kept under control condition (no contaminant addition) or exposed to a sub-lethal and environmentally relevant concentration (1 g.L−1) of SePM for 96 h. Tadpoles exposed to SePM exhibited elevated whole blood levels of Fe56, AL, Sn, Pb, Zn, Cr, Cu, Ti, Rb, V, Ce, La, Ag, As. SePM-exposed tadpoles showed a significant decrease in condition factor (12%) and increases in hepatosomatic index (25%), hemoglobin concentration (17%), and total leukocytes (82%), thrombocytes (90%), and monocytes (78%) abundance. In addition, exposed tadpoles showed higher MN and ENAs (340 and 140%, respectively) frequencies, and erythrocyte DNA damage with approximately 1.2- to 1.8-fold increases in comet parameters. Taken together, these results suggest that the multimetal mixture found in SePM is potentially genotoxic and mutagenic to L. catesbeianus tadpoles, induces stress associated with hematological changes, and negatively affects growth. Although such contamination occurs at sublethal levels, regulatory standards are needed to control the emission of SePM and protect amphibian populations.

Improvement of the Genome Editing Tools Based on 5FC/5FU Counter Selection in Clostridium acetobutylicum.

Several genetic tools have been developed for genome engineering in Clostridium acetobutylicum utilizing 5-fluorouracil (5FU) or 5-fluorocytosine (5FC) resistance as a selection method. In our group, a method based on the integration, by single crossing over, of a suicide plasmid (pCat-upp) followed by selection for the second crossing over using a counter-selectable marker (the upp gene and 5FU resistance) was recently developed for genome editing in C. acetobutylicum. This method allows genome modification without leaving any marker or scar in a strain of C. acetobutylicum that is ∆upp. Unfortunately, 5FU has strong mutagenic properties, inducing mutations in the strain's genome. After numerous applications of the pCat-upp/5FU system for genome modification in C. acetobutylicum, the CAB1060 mutant strain became entirely resistant to 5FU in the presence of the upp gene, resulting in failure when selecting on 5FU for the second crossing over. It was found that the potential repressor of the pyrimidine operon, PyrR, was mutated at position A115, leading to the 5FU resistance of the strain. To fix this problem, we created a corrective replicative plasmid expressing the pyrR gene, which was shown to restore the 5FU sensitivity of the strain. Furthermore, in order to avoid the occurrence of the problem observed with the CAB1060 strain, a preventive suicide plasmid, pCat-upp-pyrR*, was also developed, featuring the introduction of a synthetic codon-optimized pyrR gene, which was referred to as pyrR* with low nucleotide sequence homology to pyrR. Finally, to minimize the mutagenic effect of 5FU, we also improved the pCat-upp/5FU system by reducing the concentration of 5FU from 1 mM to 5 µM using a defined synthetic medium. The optimized system/conditions were used to successfully replace the ldh gene by the sadh-hydG operon to convert acetone into isopropanol.

CuO/TiO2/ZnO NPs Anchored Hydrogen Exfoliated Graphene: To Comprehend the Role of Graphene in Catalytic Reduction of p-Nitrophenol.

The present study deals with sonochemically in situ synthesis of a novel functional catalyst using hydrogen exfoliated graphene (HEG) supported titanium dioxide (TiO2) and copper sulfate (CuSO4) doped with zinc oxide (ZnO) (abbreviated as Ti/Cu/Zn-HEG). The synthesis of the Ti/Cu/Zn-HEG nanocomposite (NCs) catalyst was confirmed through its characterizations by XRD, SEM-EDX, TEM, XPS, FTIR, and BET methods. It was assessed for catalytic conversion of a model aromatic compound para-nitrophenol (p-NP) in an aqueous solution. The p-NP is a nitroaromatic compound that has a toxic and mutagenic effect. Its removal from the water system is necessary to protect the environment and living being. The newly synthesized Ti/Cu/Zn-HEG NCs were applied for their higher stability and catalytic activity as a potential candidate for reducing p-NP in practice. The operating parameters, such as p-NP concentration, catalyst dosage, and operating time were optimized for 150 ppm, 400 ppm, and 10 min through response surface methodology (RSM) in Design-Expert software to obtain the maximum reduction p-NP up to 98.4% at its normal pH of 7.1 against the controls (using HEG, Ti/Cu-HEG, and Zn-HEG). Analysis of variance of the response suggested the regression equation to be significant for the process with a major impact on catalyst concentration and operating time. The model prediction data (from RSM) and experimental data were corroborated well as reflected through model's low relative error (RE < 0.10), high regression coefficient (R2 > 0.97), and Willmott d-index (dwill-index > 0.95) values.

Mutagenic effects of a commercial glyphosate-based herbicide formulation on the soil filamentous fungus Aspergillus nidulans depending on the mode of exposure.

Glyphosate-based herbicides (GBH) are the most used pesticides worldwide. This widespread dissemination raises the question of non-target effects on a wide range of organisms, including soil micro-organisms. Despite a large body of scientific studies reporting the harmful effects of GBHs, the health and environmental safety of glyphosate and its commercial formulations remains controversial. In particular, contradictory results have been obtained on the possible genotoxicity of these herbicides depending on the organisms or biological systems tested, the modes and durations of exposure and the sensitivity of the detection technique used. We previously showed that the well-characterized soil filamentous fungus Aspergillus nidulans was highly affected by a commercial GBH formulation containing 450g/L of glyphosate (R450), even when used at doses far below the agricultural application rate. In the present study, we analysed the possible mutagenicity of R450 in A. nidulans by screening for specific mutants after different modes of exposure to the herbicide. R450 was found to exert a mutagenic effect only after repeated exposure during growth on agar-medium, and depending on the metabolic status of the tested strain. The nature of some mutants and their ability to tolerate the herbicide better than did the wild-type strain suggested that their emergence may reflect an adaptive response of the fungus to offset the herbicide effects. The use of a non-selective molecular approach, the quantitative random amplified polymorphic DNA (RAPD-qPCR), showed that R450 could also exert a mutagenic effect after a one-shot overnight exposure during growth in liquid culture. However, this effect was subtle and no longer detectable when the fungus had previously been repeatedly exposed to the herbicide on a solid medium. This indicated an elevation of the sensitivity threshold of A. nidulans to the R450 mutagenicity, and thus confirmed the adaptive capacity of the fungus to the herbicide.

Cytotoxicity, mutagenicity and genotoxicity of electronic cigarettes emission aerosols compared to cigarette smoke: the REPLICA project

Concerns have recently increased that the integrity of some scientific research is questionable due to the inability to reproduce the claimed results of some experiments and thereby confirm that the original researcher's conclusions were justified. This phenomenon has been described as 'reproducibility crisis' and affects various fields from medicine to basic applied sciences. In this context, the REPLICA project aims to replicate previously conducted in vitro studies on the toxicity of cigarette smoke and e-cigarette aerosol, sometimes adding experiments or conditions where necessary, in order to verify the robustness and replicability of the data. In this work the REPLICA Team replicated biological and toxicological assessment published by Rudd and colleagues in 2020. As in the original paper, we performed Neutral Red Uptake (NRU) assay for the evaluation of cytotoxicity, Ames test for the evaluation of mutagenesis and In Vitro Micronuclei (IVMN) assay for the evaluation of genotoxicity on cells treated with cigarette smoke or e-cigarette aerosol. The results showed high cytotoxicity, mutagenicity and genotoxicity induced by cigarette smoke, but slight or no cytotoxic, mutagenic and genotoxic effects induced by the e-cigarette aerosol. Although the two studies presented some methodological differences, the findings supported those previously presented by Rudd and colleagues.