Evaluation Of Mutagenicity Research Articles

Effect of sequencing platforms on the sensitivity of chemical mutation detection using Hawk-Seq™

BackgroundError-corrected next-generation sequencing (ecNGS) technologies have enabled the direct evaluation of genome-wide mutations after exposure to mutagens. Previously, we reported an ecNGS methodology, Hawk-Seq™, and demonstrated its utility in evaluating mutagenicity. The evaluation of technical transferability is essential to further evaluate the reliability of ecNGS-based assays. However, cutting-edge sequencing platforms are continually evolving, which can affect the sensitivity of ecNGS. Therefore, the effect of differences in sequencing instruments on mutation data quality should be evaluated.ResultsWe assessed the performance of four sequencing platforms (HiSeq2500, NovaSeq6000, NextSeq2000, and DNBSEQ-G400) with the Hawk-Seq™ protocol for mutagenicity evaluation using DNA samples from mouse bone marrow exposed to benzo[a]pyrene (BP). The overall mutation (OM) frequencies per 106 bp in vehicle-treated samples were 0.22, 0.36, 0.46, and 0.26 for HiSeq2500, NovaSeq6000, NextSeq2000, and DNBSEQ-G400, respectively. The OM frequency of NextSeq2000 was significantly higher than that of HiSeq2500, suggesting the difference to be based on the platform. The relatively higher value in NextSeq2000 was a consequence of the G:C to C:G mutations in NextSeq2000 data (0.67 per 106 G:C bp), which was higher than the mean of the four platforms by a ca. of 0.25 per 106 G:C bp. A clear dose-dependent increase in G:C to T:A mutation frequencies was observed in all four sequencing platforms after BP exposure. The cosine similarity values of the 96-dimensional trinucleotide mutation patterns between HiSeq and the three other platforms were 0.93, 0.95, and 0.92 for NovaSeq, NextSeq, and DNBSeq, respectively. These results suggest that all platforms can provide equivalent data that reflect the characteristics of the mutagens.ConclusionsAll platforms sensitively detected mutagen-induced mutations using the Hawk-Seq™ analysis. The substitution types and frequencies of the background errors differed depending on the platform. The effects of sequencing platforms on mutagenicity evaluation should be assessed before experimentation.

Mutagenicity and genotoxicity evaluation of 15 nitrosamine drug substance-related impurities in human TK6 cells

Nitrosamine drug substance-related impurities (NDSRIs) are a sub-category of N-nitrosamine drug impurities that share structural similarity to the corresponding active pharmaceutical ingredient. The mutagenicity of NDSRIs is poorly understood. We previously tested a series of NDSRIs using the Enhanced Ames Test (EAT). In this follow-up study, we further examined the genotoxicity and mutagenicity of 15 of these NDSRIs in human TK6 cells. Seven EAT-positive NDSRIs, including N-nitroso-nortriptyline, N-nitroso-fluoxetine, N-nitroso-desmethyl-diphenhydramine, N-nitroso-duloxetine, N-nitroso-lorcaserin, N-nitroso-varenicline, and N-nitroso-sertraline, induced concentration-dependent increases in micronuclei after bioactivation with hamster liver S9. These NDSRIs were also mutagenic in the TK and HPRT gene mutation assays, consistent with their positive EAT results. In the presence of hamster liver S9, the eight EAT-negative NDSRIs were negative in the micronucleus assay and negative for mutation induction. Using TK6 cells endogenously expressing a single human cytochrome P450 (CYP), we found that CYP2C19, CYP2B6, CYP2A6, and CYP3A4 are key enzymes activating the genotoxicity and mutagenicity of these NDSRIs. Overall, the hamster S9-mediated TK6 cell mutagenicity results agreed with those observed in the EAT, indicating consistency in the mutagenic responses produced by NDSRIs across different testing systems. These data support the use of EAT for hazard identification and safety assessment of NDSRIs.

Mutagenicity evaluation of methyl tertiary- butyl ether in multiple tissues of transgenic rats following whole body inhalation exposure.

Methyl tertiary-butyl ether (MTBE) is used as a component of motor vehicle fuel to enhance combustion efficiency and to reduce emissions of carbon monoxide and nitrogen oxides. Although MTBE was largely negative in the in vitro and in vivo genotoxicity studies, isolated reports of positive findings along with the observation of tumors in the rat cancer bioassays raised concern for its in vivo mutagenic potential. To investigate this, transgenic male Big Blue Fischer 344 rats were exposed to 0 (negative control), 400, 1000, and 3000 ppm MTBE via whole body inhalation for 28 consecutive days, 6 h/day. Mutant frequencies (MF) at the cII locus of the transgene in the nasal epithelium (portal of entry tissue), liver (site of primary metabolism), bone marrow (rapidly proliferating tissue), and kidney (tumor target) were analyzed (5 rats/exposure group) following a 3-day post-exposure manifestation period. MTBE did not induce a mutagenic response in any of the tissues investigated. The adequacy of the experimental conditions to detect induced mutations was confirmed by utilizing tissue samples from animals treated with the known mutagen ethyl nitrosourea. These data provide support to the conclusion that MTBE is not an in vivo mutagen and male rat kidney tumors are not likely the result of a mutagenic mode of action.

DeepRA: A novel deep learning-read-across framework and its application in non-sugar sweeteners mutagenicity prediction

Non-sugar sweeteners (NSSs) or artificial sweeteners have long been used as food chemicals since World War II. NSSs, however, also raise a concern about their mutagenicity. Evaluating the mutagenic ability of NSSs is crucial for food safety; this step is needed for every new chemical registration in the food and pharmaceutical industries. A computational assessment provides less time, money, and involved animals than the in vivo experiments; thus, this study developed a novel computational method from an ensemble convolutional deep neural network and read-across algorithms, called DeepRA, to classify the mutagenicity of chemicals. The mutagenicity data were obtained from the curated Ames test data set. The DeepRA model was developed using both molecular descriptors and molecular fingerprints. The obtained DeepRA model provides accurate and reliable mutagenicity classification through an independent test set. This model was then used to examine the NSSs-related chemicals, enabling the evaluation of mutagenicity from the NSSs-like substances. Finally, this model was publicly available at https://github.com/taraponglab/deepra for further use in chemical regulation and risk assessment.

Assessment of Acute and Chronic Toxicity in Wistar Rats (Rattus norvegicus) and New Zealand Rabbits (Oryctolagus cuniculus) of an Enriched Polyphenol Extract Obtained from Caesalpinia spinosa.

Although herbal drugs are often considered safe for consumption, there is increasing evidence that some can generate undesirable health effects. However, polyphenols found in certain plants have been shown to provide a range of benefits for human health. In previous work, a standardized and quantified extract (P2Et) obtained from Caesalpinia spinosa (Dividivi) plant showed promising antioxidant, immunomodulatory, and anti-inflammatory properties in animal models of cancer and COVID-19 patients. The extract has also been subjected to genotoxicity, mutagenicity, and 28-day oral chronic toxicity evaluations, demonstrating a good safety profile. To advance preclinical and clinical development, further acute and chronic toxicity evaluations of the P2Et extract were performed. Acute toxicity tests were performed orally in Wistar rats at a dose of 2000 mg/kg, indicating that the lethal dose 50% (LD50) value exceeded 2000 mg/kg and classifying the P2Et extract as category 5 according to the Globally Harmonized System of Classification (GHS). In this work, chronic toxicity tests were conducted for 180 days on Wistar rats and New Zealand rabbits at a dose of 1000 mg/kg under Good Laboratory Practice (GLP) conditions. No weight loss or alterations in biochemical and hematological parameters associated with treatment were observed in the animals, suggesting the absence of toxicity in the assessed parameters. These results indicate that the P2Et extract is safe for oral administration at doses up to 1000 mg/kg body weight over a six-month period.

Mutagenicity and safety evaluation of Ashwagandha (Withania somnifera) root aqueous extract in different models

Withania somnifera (Ashwagandha) also called as Indian ginseng, a revered herb from Indian traditional system of medicine is a rejuvenator and tonic (Rasayana) used for its varied benefits. The roots of ashwagandha exhibit properties like anti-inflammatory, aphrodisiac, anthelmintic, astringent, diuretic, stimulant and thermogenic. However, data of ashwagandha on its mutagenic effects are lacking. In the present study, in-vitro genotoxicity tests were used to evaluate the mutagenic potential of Ashwagandha Root Extract (ARE). Concentrations of 0.156 to 5.00 mg/plate ARE were used for conducting Bacterial reverse mutation test (BRMT). For chromosome aberration (CA) test ARE was used in concentrations of 0.25 to 2.00 mg/ml, and for micronucleus (MN) tests ARE concentrations of 500/1000/2000 mg/kg were used. Acute oral toxicity was conducted in Wistar rats (n = 25) as per the OECD guideline (#423) with doses of 500/1000/2000 mg/kg body weight in male Swiss albino mice for morbidity and mortality for 3 days. The BRMT and CA tests were conducted with and without metabolic activation (S9). The study was approved by the institutional ethics committee (IEC) and institutional animal ethics committee (IAEC). ARE failed to show any mutagenic effects up to a dose of 5 mg/plate in BRMT. Also, ARE did not show any clastogenic activity in doses up to 2 mg/ml in CA test and in micronucleus test up to 2000 mg/kg body weight. These results were observed with and without metabolic activation (S9) under the stated experimental conditions. No mortality, morbidity, or any clinical signs were observed up to 3 days following ARE administration. Ashwagandha root extract failed to show any mortality in doses up to 2000 mg/kg oral dosage and did not show any mutagenic (genotoxic) effects in high concentrations.

Direct Impact of the Air on Mutant Cells for Mutagenicity Assessments in Urban Environments.

Urban air pollution is recognized as a critical problem for public health and is classified as a carcinogen for humans. A great number of studies have focused on the monitoring of urban air mutagenicity. One of the best-known and applied methods for assessing mutagenicity is the Ames test, a bacterial reverse mutation test. The classic protocol for assessing air mutagenicity involves the concentration of particulate matter (PM) on filters and subsequent extraction using organic solvents. This work aimed to develop a method for the evaluation of air mutagenicity directly impacted by air on microbial plates already containing an Ames' microbial sensor. A specific six-month sampling campaign was carried out in Turin in a period with high air pollution. Samples were tested for mutagenicity on Salmonella typhimurium strains TA98, TA100, and YG1024 with the traditional method and with the new direct method. The new protocol is able to evaluate the mutagenicity of the sampled air and obtain repeatable results. The final sensitivity is similar to the traditional method (≈10 net revertants/m3); however, the mutagenic response is due to the complete air pollution mixture, including volatile and semivolatile pollutants avoiding the concentration of filters and the following laborious extraction procedures. Despite some critical issues in contamination control, the method is easier, faster, and less expensive than traditional methods.

Chemical, ecotoxicological, cytotoxic, and mutagenic evaluation of gelling agents used in the production of 70% alcohol gel

With COVID-19, there has been an increase in the use of gelling agents for hand sanitizer production, and as a result, the release of this product into wastewater could induce impacts and adverse reactions in living organisms. Thus, ecotoxicological and cytotoxicological assessments of gelling agents with test organisms from different trophic levels are necessary to assess their environmental safety. For this, seven cellulose-based gelling agents and a polyacrylic acid derivative (C940) were selected for tests with Artemia salina. The most toxic agent was tested on Allium cepa to assess cytotoxicity. The volatile compounds of the gelling agents were analyzed. Cellulose-based gelling agents were not considered toxic according to their LC50, but C940 presented moderate toxicity to A. salina and cytotoxicity to Allium cepa, but without mutagenicity. In addition, C940 contained cyclohexane as a volatile compound. Thus, cellulose-based gelling agents are better environmental options than carbomer for 70% alcohol gel sanitizer.

Genotoxic and mutagenic evaluation in Eisenia foetida annelids exposed to iron ore tailings from the region of Brumadinho, MG, Brazil

Soils that have a disproportion of metallic elements due to anthropic activities endanger the terrestrial fauna. This study evaluated whether earthworms (Eisenia foetida) exposed to ore tailings from Brumadinho region presented a higher frequency of genotoxic and mutagenic damages than annelids from a reference area (control). The animals were exposed to substrates containing 0%, 25%, 50%, 75%, and 100% iron mining waste. The results indicated increased DNA damage (p < 0.05), detected by the comet assay at 25% and 50%. There was a three-fold increase in micronuclei in animals on the substrates with the highest concentrations (75% and 100%) [F = 3.095; p = 0.02]. The earthworms lost weight as the percentage of mining waste increased. We concluded that E. foetida presented DNA damage in the contaminated soils of Brumadinho. However, more research is fundamental, once the environmental disaster in Brumadinho was one of the biggest mining catastrophe in Brazil.

Evaluation of toxicity and mutagenicity of oxaliplatin on germ cells in an alternative in vivo model Caenorhabditis elegans.

The platinum compound oxaliplatin is a widely used chemotherapeutic drug that shows a broad spectrum of activity in various human tumors. While the treatment-related side effects of oxaliplatin on directly treated individuals have been well-documented, little is known about the influence of oxaliplatin on germ cells and non-exposed progenies. Here we investigated the reproductive toxicity of oxaliplatin in a 3R-compliant in vivo model Caenorhabditis elegans, and evaluated the germ cell mutagenicity of oxaliplatin by using whole genome sequencing. Our results indicated that oxaliplatin treatment significantly disrupts development of spermatids and oocytes. By treating parental worms with oxaliplatin for three successive generations, sequencing data unveiled the mutagenic effects of oxaliplatin on germ cells. Analysis of genome-wide mutation spectra showed the preferentially induction of indels by oxaliplatin. In addition, we uncovered the involvement of translesion synthesis polymerase ζ in modulating mutagenic effects of oxaliplatin. These findings suggest that germ cell mutagenicity is worthy of consideration for the health risk assessment of chemotherapeutic drugs, while the combined use of alternative in vivo models and next generation sequencing technology appears to be a promising way for the preliminary safety assessment of various drugs.

The absence of genotoxicity of Aloe vera beverages: A review of the literature.

Aloe has a long history of topical and systemic use with testimonials of countless health benefits and is one of the most popular botanical medicines in the world for the management of a wide variety both of benign and serious ailments including irritable bowel syndromes, osteoarthritis, Type II diabetes mellitus, and viral respiratory illness. The human consumption of Aloe vera extract in beverage form has substantially grown over the last several decades, in no small part, due to the increased consumer interest in alternative approaches to health benefits. The principal aim of the present paper is to characterize the research to date that has explored the genotoxic potential of Aloe vera inner leaf gel extract and decolorized whole leaf extract used in commercially available food-grade drinkable products which contain no more than 10ppm aloin. Despite prevailing public health opinion, especially in Europe, the consensus of the reviewed studies retrieved from the peer-reviewed literature together with a mutagenic evaluation of an Aloe vera whole leaf decolorized spray-dried powder is that these products are not genotoxic.

Prioritization of mycotoxins based on mutagenicity and carcinogenicity evaluation using combined in silico QSAR methods

Mycotoxins and their metabolites are a family of compounds that contains a great diversity of both structure and biological properties. Information on their toxicity is spread within several databases and in scientific literature. Due to the number of molecules and their structure diversity, the cost and time required for hazard evaluation of each compound is unrealistic.In that purpose, new approach methodologies (NAMs) can be applied to evaluate such large set of molecules. Among them, quantitative structure-activity relationship (QSAR) in silico models could be useful to predict the mutagenic and carcinogenic properties of mycotoxins.First, a complete list of 904 mycotoxins and metabolites was built. Then, some known mycotoxins were used to determine the best QSAR tools for mutagenicity and carcinogenicity predictions. The best tool was further applied to the whole list of 904 mycotoxins. At the end, 95 mycotoxins were identified as both mutagen and carcinogen and should be prioritized for further evaluation.

New possibilities of the Ames test for evaluation of mutagenicity of technical products of active ingredients of pesticides

Introduction. The Ames test is the one of the most popular methods for mutagenicity evaluation of environmental factors. In some cases, this method is suggested to be the only and sufficient assay for the first stage of the equivalence assessment of pesticide technical grade active ingredients (TGAI) to the original products. A limitation of the Ames test is related to the impossibility of an objective equivalence assessment of some cytotoxic TGAIs, in particular, sulfonylureas, and triazolpyrimidines. Based on the mode of action of the pesticides belongs to these chemical classes, we suggested a modification of the plate incorporation method protocol of the Ames test to the increase of maximal non-cytotoxic concentration up to the 5 mg/plate recommended by regulatory documents. Materials and methods. The five strains of Salmonella typhimurium TA98, TA100, TA1535, TA97, TA102 were used. The modification of the protocol included a supplementation of the top agar with isoleucine (1-5 mM). Results. The maximum non-cytotoxic concentrations of thifensulfuron-methyl and florasulam using the standard top agar did not exceed 0.05-0.125 mg/plate. The enrichment of the top agar with isoleucine allowed evaluating the mutagenicity of the substances up to the maximal recommended concentration of 5.0 mg/plate. The number of spontaneous revertants was within the historical limits of the laboratory control obtained under standard conditions. Positive controls showed pronounced mutagenic effects in case of all strains with and without metabolic activation (p≤0.05). Limitations. Mutagenicity was evaluated only for TGAIs, which are acetohydroxyacid synthase inhibitors. Conclusion. The application of the modified Ames test protocol for mutagenicity assessment of TGAIs from the classes of sulfonylureas and triazolpyrimidines under supplementation of the top agar with isoleucine is a more objective way to evaluate their mutagenicity. The proposed protocol expands the possibilities of revealing dangerous mutagenic impurities that may occur in TGAIs in the small quantities, and after entering the environment can cause the gain in the mutation level in living organisms.

Cytotoxicity, oral toxicity, genotoxicity, and mutagenicity evaluation of essential oil from Psidium glaziovianum Kiaersk leaves

Ethnopharmacological relevanceMembers of the Psidium genus have been suggested in ethnobotanical research for the treatment of various human diseases, and some studies have already proven their popular uses through research, such as Psidium glaziovianum, which is found in Brazil's northeast and southeast regions and has antinociceptive and anti-inflammatory properties; however, the safety of use has not yet been evaluated. Aim of the studyThis study investigated the safety of using essential oil obtained from P. glaziovianum leaves (PgEO) in vitro and in vivo models. Materials and methodsCytotoxicity was evaluated in murine erythrocytes, while acute toxicity, genotoxicity (comet assay) and mutagenicity (micronucleus test) studies were performed using Swiss albino mice. ResultsIn the cytotoxicity assay, the hemolysis rate indicated a low capacity of PgEO to cause cell lysis (0.33–1.78%). In the acute oral toxicity study, animals treated with up to up to 5000 mg/kg body weight did not observe mortality or physiological changes. Neither dosage caused behavioral problems or death in mice over 14 days. The control and 2,000 mg/kg groups had higher feed intake and body weight than the 5,000 mg/kg PgEO group. Erythrocyte count, hemoglobin level, mean corpuscular volume, and MCV decreased, but serum alanine and aspartate aminotransferases increased. In the genotoxic evaluation, 5000 mg/kg PgEO enhanced nucleated blood cell DI and DF. ConclusionsThe present study describes that PgEO can be considered well tolerated in acute exposure at doses up to 2000 mg/kg, however the dose of 5000 mg/kg of PgEO should be used with caution.

Evaluation of Mutagenicity and Anti-Mutagenicity of Various Bean Milks Using Drosophila with High Bioactivation.

The consumption of a nutritious diet including phytochemicals can minimize mutations as the primary cause of carcinogenesis. Bean consumption supplies calories, minerals and phytochemicals but their anti-mutagenic properties in vivo remain little understood. Hence, the present study aimed to study the mutagenicity and anti-mutagenic properties of five bean milks using the somatic mutation and recombination test (SMART) involving Drosophila with high bioactivation. Milk derived from five bean varieties, namely black bean (Phaseolus vulgaris), red kidney bean (Phaseolus vulgaris), mung bean (Phaseolus aureus), peanut (Arachis hypogaea) and soybean (Glycine max) did not induce DNA mutations in Drosophila with high bioactivation, indicating their genome-safe properties. All bean milks showed anti-mutagenicity against the food-derived mutagen, urethane, in vivo with different degrees of inhibition. In the co-administration study, larvae were treated with each bean milk together with urethane. Soybean milk showed the highest anti-mutagenicity at 27.75%; peanut milk exhibited the lowest at 7.51%. In the pre-feeding study, the larvae received each bean milk followed by urethane. Soybean milk exhibited the highest anti-mutagenic potential, followed by red kidney bean and black bean milks. Total phenolic and antioxidant data revealed that the anti-mutagenicity of both red kidney bean milk and black bean milk might be derived from their phenolic or antioxidant properties; other phytochemicals may contribute to the high anti-mutagenicity observed in soybean milk. Further investigations on the anti-mutagenicity of bean milks against other dietary mutagens are required to develop bean-based products with potent anti-mutagenic properties.

Evaluation of physical and chemical mutagens on various genotypes of brinjal (Solanum melongena L.) in M2 generation

Mutation breeding in crop plants such as brinjal (Solanummelongena L.) is a successful approach in change of producthaving narrow genetic base and to explore it a field experimentwas conducted toevaluate the effect of physical mutagensuch as gamma rays and chemical mutagens such as Ethylmethane sulphonate (EMS) were used on two brinjalgenotypes namely Banarasi Gol and Kashi Taru. The seedswere treated with different concentrations of gammairradiation (5, 10, 15 and 20 kR) and EMS (0.05, 0.10, 0.15 and0.20%).The increasing concentration of mutagens wasrecorded with a negative response on all growth and yieldattributes of both the genotypes which ultimately reducethe yield. In this context the 5kR gamma rays and 0.05%EMS concentration were recorded with superior values ofall characters in M2 generation. Early flowering and earlyedible fruit maturity was observed under 5kR gamma raysover all other treatments. The fruit yield per plant increasedby 19.87% and 20.30% of Banarasi Gol and Kashi Taru,respectively under 5kR gamma rays over control. Lowestvalue of all characters was recorded under 0.20% EMS ascompared to all other treatments including control. Thus itcan be concluded on present study basis that the increasingconcentration of mutagens were showed an adverse effectfor all characters.

Thymidine Kinase+/- Mammalian Cell Mutagenicity Assays for Assessment of Nanomaterials.

The methods outlined here are part of a series of papers designed specifically for genotoxicity assessment of nanomaterials (NM). Common Considerations such as NM characterization, sample preparation and dose selection, relevant to all genotoxicity assays, are found in an accompanying paper. The present paper describes methods for evaluation of mutagenicity in the mammalian (mouse) thymidine kinase (Tk) gene occurring in L5178Y mouse lymphoma (ML) cells and in the designated TK gene in human lymphoblastoid TK6 cells. Mutations change the functional genotype from TK+/- to TK-/-, detectable as cells surviving on media selective for the lack of thymidine kinase (TK) function. Unlike cells with TK enzyme function, the TK-/- cells are unable to integrate the toxic selection agent, allowing these cells to survive as rare mutant colonies. The ML assay has been shown to detect a broad spectrum of genetic damage, including both small scale (point) mutations and chromosomal alterations. This assay is a widely used mammalian cell gene mutation assay for regulatory purposes and is included in the core battery of genotoxicity tests for regulatory decision-making. The TK6 assay is an assay using a human cell line derived similarly via mutagenic manipulations and optimal selection. Details are provided on the materials required, cell culture methods, selection of test chemical concentrations, cytotoxicity, treatment time, mutation expression, cloning, and data calculation and interpretation. The methods describe the microwell plate version of the assays without metabolic activation.

Safety evaluation of mutagenicity, genotoxicity, and cytotoxicity of Lactobacillus spp. isolates as probiotic candidates.

BackgroundProbiotics promote a healthy balance of gut bacteria and have many beneficial effects on human digestive physiology. Although, few side effects of probiotics have been reported. This study aimed to assess the safety of five probiotic candidate Lactobacillus strains isolated from healthy individuals by examining mutagenicity, genotoxicity, and oral toxic effects.MethodsFive selected candidate probiotic (SCPs) strains were evaluated for genotoxicity (Ames test with Salmonella typhimurium), in vitro mammalian chromosome aberration test and an in vivo mouse micronucleus assay on peripheral blood of mice. To evaluate the oral dose toxicity, BALB/c mice models were treated repeatedly (2000, 1000, and 500 mg/kg body weight /day) for 28‐days.ResultsThe Ames test performed for two S. typhimurium strains TA 98 and TA100 (both in the absence and in the presence of S‐9 metabolic activation system) did not show an increase in reverse mutation because of exposure to the SCPs in any of the doses (5.0, 2.5, 1.25, 0.625, and 0.3125 mg/plate). There was no genotoxicity in the SCPs treatment in the vitro chromosome aberration assay with Chinese hamster ovary cells (CHO‐K1). In addition, none of the tested strains increased the frequency of micronucleated reticulocytes in reticulocytes, the SCPs with the studied doses caused no substantial variation in the experimental groups compared to the negative control group (p > 0.05). SCPs were not acutely toxic when administered to male and female BALB/c mice by single gavage at (2000, 1000, and 500 mg/kg b.w/day) with no mortality or clinical signs, change in body weight or macroscopic abnormalities were observed in this dose range.ConclusionAs a result, SCPs did not induce mutagenic potential in vitro with bacterial reverse mutation, clastogenicity, and in vivo tests in the ranges of concentrations evaluated in our study.

Evaluation of Mutagenicity of Covid-19 Virus And The Effect Of Morphine In Its Treatment

Because the covid-19 virus is amazingly mutating, we urgently need a lot of articles in this area. In light of recent events, we have been writing an article on the mutagenicity of the covid-19 virus and treatment with morphine. The covid-19 virus is an exception due to its non-segmented genome, its mutagenicity. Also in this article morphine is a suitable drug because it neutralizes most of the symptoms of the covid-19 virus. Morphine increases immunity against the virus due to the presence of mu3 receptors on the surface of immune cells. Morphine also counteracts symptoms such as shortness of breath, pain, and even diarrhea. Diarrhea has been reported in cases of the covid-19 virus.

In vivo mutagenic effects and oxidative stress parameters evaluation of cypermethrin and benzoate of emamectin and their mixtures in female mice

We evaluated the biological effects of ingestion by gavage, for 28 days, of the pesticides cypermethrin (CP) and emamectin benzoate (EB) and their mixtures in female Swiss mice. The groups were Control (water); CP; EB and three distinct concentrations of CP and EB mixture expressed in mg/kg/day. The biological effects were analyzed in the complete blood count and plasma (alkaline phosphatase (ALP), alanine aminotransferase (ALT) and creatinine); the biochemical parameters of oxidative stress (substances reactive to thiobarbituric acid (TBARS); reduced glutathione (GSH); catalase (CAT), superoxide dismutase (SOD) and glutathione-S-transferase (GST)), and bone marrow cells obtained from the femur for the micronucleus (MN) test. In the heart, there was a reduction in GSH in the groups (0.5 + 0.67 and 2.5 + 3.37), although in the brain this effect appeared for the other groups, except EB. Brain TBARS increased in CP and in the group (2.5 + 3.37) and platelets increased in the group (12.5 + 16.87). Genotoxic/mutagenic effects, showing a consistent increase dose-dependent effect on micronucleus counting for in the female mice. After 28 days of treatment, we can observe that the pesticide mixtures promoted genotoxic damage and oxidative brain damage in female mice, which can damage the health of these animals and possibly their future offspring.