Mutagenic Effects Research Articles

Short-Term Exposure to Benzo(a)Pyrene Causes Disruption of GnRH Network in Zebrafish Embryos.

Benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon, is considered a common endocrine disrupting chemical (EDC) with mutagenic and carcinogenic effects. In this work, we evaluated the effects of BaP on the hypothalamo-pituitary-gonadal axis (HPG) of zebrafish embryos. The embryos were treated with 5 and 50 nM BaP from 2.5 to 72 hours post-fertilization (hpf) and obtained data were compared with those from controls. We followed the entire development of gonadotropin releasing hormone (GnRH3) neurons that start to proliferate from the olfactory region at 36 hpf, migrate at 48 hpf and then reach the pre-optic area and the hypothalamus at 72 hpf. Interestingly, we observed a compromised neuronal architecture of the GnRH3 network after the administration of 5 and 50 nM BaP. Given the toxicity of this compound, we evaluated the expression of genes involved in antioxidant activity, oxidative DNA damage and apoptosis and we found an upregulation of these pathways. Consequently, we performed a TUNEL assay and we confirmed an increment of cell death in brain of embryos treated with BaP. In conclusion our data reveal that short-term exposure of zebrafish embryos to BaP affects GnRH3 development likely through a neurotoxic mechanism.

Genome damage accumulated in seed ageing leads to plant genome instability and growth inhibition.

Successful germination and seedling establishment are important determinants of crop yields and plant survival in natural environments. Germination potential is compromised by suboptimal environmental conditions that result in seed ageing and high levels of genome damage. However, the mutagenic and growth inhibitory potential of DNA damage accumulated in seeds on subsequent seedling growth remains largely unknown. Arabidopsis seeds deficient in the chromosomal break repair factors DNA LIGASE 4 and DNA LIGASE 6 exhibited hypersensitivity to the effects of natural ageing, with reduced germination vigour and seedling biomass relative to wild type seed. Here we identify that aged Arabidopsis seed display elevated levels of programmed cell death (PCD) in the root meristem which persists into seedling establishment, with higher levels of cell death in lines deficient in DNA double strand break repair. Reporter lines determined the effects of seed ageing on mutation levels and intrachromosomal recombination frequencies. Seed deterioration resulted in strikingly elevated levels of frameshift mutations and genome instability in germinated seedlings. Thus, elevated levels genome damage incurred in the seed stage of the plant life cycle potentially impacts significantly on subsequent plant development. Furthermore, the mutagenic effects of seed ageing has potentially long-term implications on the genome stability of plant populations and ecosystem fitness. Collectively, we identify genome damage accumulated in suboptimal quality seed impacts on subsequent plant growth and genome stability, with associated implications for crop yields and plant survival under changing climates.

Abstract 5156: The mutagenic effects of APOBEC3A and APOBEC3B in urothelial carcinoma

Abstract APOBEC3A (A3A) and APOBEC3B (A3B) are members of a family of cytidine deaminase enzymes that catalyze the removal of an amino group from cytosine nucleotides generating an uracil in its place that serve as a source of mutations. The resulting C→U transition has been linked to various oncogenic mutations, most predominately in bladder cancer. While both A3A and A3B activity can account for widespread changes to the genomic landscape, prior studies have shown tumor specific effects. In hepatocellular carcinoma, A3A has been shown to be the only APOBEC3 family member capable of driving tumor formation in the presence of p53 downregulation, while studies in breast cancer have suggested A3B as a driver of tamoxifen resistance. Currently, it is unclear if both A3A and A3B drive APOBEC-induced mutagenesis in bladder cancer, or if one enzyme plays a larger mutagenic role than the other. In urothelial carcinoma, there has not been a direct comparison of A3A and A3B mutagenic activity, highlighting the need to determine the effects of each respective enzyme. To explore the effects of A3A and A3B enzymes, we accessed publicly available single cell RNA (scRNA seq) data of tumor samples from 8 bladder cancer patients. Analysis from scRNA seq data revealed an enrichment of A3A expression in both monocyte and urothelial cell populations, while A3B expression is primarily restricted to urothelial cells, suggesting a cell type specific functional difference between A3A and A3B in bladder cancer. Immunogenomic analysis of TCGA bladder cancer tumors stratified by APOBEC mutational load (High, Low, No) showed that tumors with APOBEC high mutational load had high levels of interferon gamma response, lymphocyte infiltration signature score, M1 macrophages, intratumor heterogeneity, and stromal fraction compared to tumors with low APOBEC mutational load. In addition, increases in features of genomic instability was observed in tumors with high APOBEC mutational load. Interestingly, we saw unique correlations of A3A and A3B in TCGA bladder tumors. A3A expression correlated with characteristics of an inflamed tumor microenvironment while A3B expression correlated with features of genomic instability. To elucidate the divergent effects of A3A and A3B independently, we have generated isogenic mouse bladder cancer cell lines that overexpress HA tagged A3A and A3B, to directly compare their mutagenic effects through in-vitro and in-vivo experiments. We have validated through deamination assays, the functionality of A3B in these cell lines. In silico data has shown differential roles for A3A and A3B as it relates to the tumor/immune environment; we hypothesize that this might result in subunit specific response and resistance to anti-PD-1 immunotherapy. Elucidation of the A3 specific driver of APOBEC mutagenesis in urothelial carcinoma will help identity a predictive and/or prognostic biomarker to anti-PD-1 checkpoint immune inhibition. Citation Format: Michael S. Sturdivant, Andrew S. Truong, Mi Zhou, Jeffrey S. Damrauer, William Y. Kim. The mutagenic effects of APOBEC3A and APOBEC3B in urothelial carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5156.

Chemical characterization of Brazilian savannah Byrsonima species (muricis) and their impact on genomic instability and chemopreventive effects

The identification of new drugs with few or no adverse effects is of great interest worldwide. In cancer therapy, natural products have been used as chemopreventive and chemotherapeutic agents. Plants from the Brazilian savannah belonging to the Byrsonima genus are popularly known as muricis and have attracted much attention due to their various pharmacological activities. However, there are currently no data on these plants concerning their use as chemopreventive or chemotherapeutic agents in human cell lines. The present study assessed the potential of B. correifolia, B. verbascifolia, B. crassifolia, and B. intermedia extracts as natural alternatives in the prevention and/or treatment of cancer. The chemical constituents present in each extract were analyzed by electrospray ionization-mass spectrometry (ESI-MSN). The mutagenic/antimutagenic (micronucleus assay), genotoxic/antigenotoxic (comet assay), apoptotic/necrotic (acridine orange/ethidium bromide uptake), and oxidative/antioxidative (CM-H2DCFDA) effects of the extracts and their influence on gene expression (RTqPCR) were investigated in nonmetabolizing gastric (MNP01) and metabolizing hepatocarcinoma (HepG2) epithelial cells to evaluate the effects of metabolism on the biological activities of the extracts. The genotoxicity, mutagenicity, and apoptotic effects observed in HepG2 cells with B. correifolia and B. verbascifolia extracts are probably associated with the presence of proanthocyanidins and amentoflavone. In MNP01 cells, none of the four extracts showed mutagenic effects. B. crassifolia and B. intermedia extracts exhibited strong antimutagenicity and enhanced detoxification in HepG2 cells and antioxidant capacities in both types of cells, possibly due to the presence of gallic and quinic acids, which possess chemopreventive properties. This study identifies for the first time B. correifolia and B. verbascifolia extracts as potential agents against hepatocarcinoma and B. crassifolia and B. intermedia extracts as putative chemopreventive agents.

Inactive doses of oxathiine derivative on long-term effects of the organism

Introduction. The study of the effects of the long-term effect of the active substances of pesticides on the body of warm-blooded animals is an obligatory stage 
 of their comprehensive toxicological and hygienic assessment.
 The aim of the study was to establish the levels of inactive doses of the effects of the long-term (NOEL) action of a compound of the oxatiine class.
 Materials and methods. In accordance with the planned purpose of the study in the biological testing laboratory of the Federal Scientific Center of Hygiene named after F.F. Erisman of the Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing еxperiments were conducted to establish the parameters of acute oral toxicity, the presence of possible teratogenic and embryotoxic effects, and the effect on the reproductive function 
 of a technical product of the oxatiin class (TPO) on the body of warm-blooded (rats). Previously, studies in this volume have not been conducted.
 Results. LD50 of the studied compound with a single oral administration to male rats is more than 4500 mg/kg of body weight. When studying the embryotoxic effect, the inactive dose for the maternal organism and offspring is set at the level of – 1/52 LD50; the inactive dose for the teratogenic effect for the maternal organism is 1/52 LD50, offspring – 1/27 LD50. As a result of studying the effect of the oxatiine derivative on the indicators of reproductive function, the inactive dose for maternal, paternal organisms, and offspring, is 1/313 LD50.
 Limitations. In our study to establish the levels of inactive doses of the long-term effects of toxicity of a technical product derived from oxatiines, there are no data on the results of the mutagenic effect of the studied compound on the body of warm-blooded (rats, mice).
 Conclusion. It has been established that according to the “Hygienic classification of pesticides and agrochemicals according to the degree of danger” (Methodological Recommendations of MP No. 1.2.0235-21* dated 02/15/2022), the studied chemical product belongs to the 4th hazard class for acute oral toxicity (LD50) and teratogenic effect (low-hazard compound; for embryotoxic effect and reproductive toxicity to the 3rd hazard class (moderately dangerous compound).

Evaluation of informativeness of mutation groups of Nigella damascena L. M2 generation

Purpose. To carry out a mathematical and statistical evaluation of the mutagenesis data of the M2 generation of Nigella damascena varieties ‘Berehynia’ and ‘Charivnytsia’ in order to identify relationships between groups of mutations and mathematical justification of their use in the process of further analysis and selection of hereditary changes of mutant plants. Methods. Seeds of the varieties ‘Berehynia’ and ‘Charivnytsia’ were treated with chemical mutagens. The mutations identified by visual observation of the plants at different stages of their growth and development were divided into eight groups. In each group of each treatment option, the frequency of mutations was calculated as a function of the type of mutagen, its concentration and exposure time. The mathematical and statistical evaluation of the results was carried out using the MS Excel analysis package and Spearman’s rank correlation. Results. The mutational difference in the M2 generation between eight groups of Nigella damascena varieties ‘Berehynia’ and ‘Charivnytsia’ under the influence of the mutagens ethyl methanesulfonate, nitrosomethylurea and the new chemical mutagen DG-2 (a complex of 3-N,N-dimethylamino sulfonane with dimethyl) was identified and evaluated. It was found that the correlation value of the mutagenic effects ranged from 0.437 to 0.752 with significance levels from 3.540 ´ 10–5 to 0.037. The following groups of mutations can be considered informative: stem, shoot and leaf structures; flower structure; colour of the corolla petals; structure of the capsule; physio­logical changes in the process of growth and development. Conclusions. The effect of the mutagens EMS, NMU in concentrations of 0.01 and 0.05% and DG-2 in concentrations of 0.5 and 0.05% was determined on Nigella damascena varieties ‘Berehynia’ and ‘Charivnytsia’ after exposure for 6 and 16 hours. Mutations in the structure of the stem, shoots and leaves, the colour of the petals of the corolla, the structure of the flower and capsule, and those causing a violation of chlorophyll synthesis should be considered informative.

Оценка мутагенного эффекта проб воды и почвы, собранных вблизи бывших хранилищ хлорорганических пестицидов в Жамбылском районе Алматинской области с использованием различных модельных тест-систем

Устаревшие хлорорганические пестициды в настоящее время запрещены как стойкие органические загрязнители окружающей среды. Не утилизированные должным образом, они продолжают загря з-нять почву и воду, накапливаться в пищевой цепи и наносить вред растениям, животным и организму человека. Цель исследования — оценить загрязнение воды и почвы вокруг складов неутилизирован-ными запрещенными хлорорганическими пестицидами и их возможное генотоксическое действие. Были обследованы бывшие склады пестицидов в двух поселках Жамбылского района Алматинской области. Химический анализ показал загрязнение почвы вокруг складов хлорорганическими пестици-дами и тяжелыми металлами. Пробы воды и почвы, отобранные вблизи хранилищ, использовались для оценки экологического риска. Генотоксическое действие проб воды и почвы оценивали на раз-личных модельных объектах: Salmonella typhimurium, Drosophila melanogaster, Allium cepa, культурах лимфоцитов овец и человека. Было обнаружено, что образцы воды и почвы вызывали слабый мута-генный эффект во всех модельных системах, увеличивая частоту мутаций и хромосомных аберраций. Хотя генотоксический эффект был продемонстрирован для каждой из моделей, разные модели пока-зали разную чувствительность к действию пестицидов и разную степень реакции. Поэтому для адек-ватной оценки мутагенности пестицидов необходимо применять батарею тестов с разными модельными объектами. Результаты исследований показали, что остатки устаревших пестицидов по-прежнему загрязняют окружающую среду и должны быть своевременно утилизированы безопасным способом, чтобы избежать загрязнения окружающей среды.

Induction of clastogenesis and gene mutations by carbamazepine (at its therapeutically effective serum levels) in mammalian cells and the dependence on human CYP2B6 enzyme activity

Carbamazepine (CBZ, an antiepileptic) is metabolized by multiple CYP enzymes to its epoxide and hydroxides; however, whether it is genotoxic remains unclear. In this study, molecular docking (CBZ to CYPs) and cytogenotoxic toxicity assays were employed to investigate the activation of CBZ for mutagenic effects, in various mammalian cell models. Docking results indicated that CBZ was valid as a substrate of human CYP2B6 and 2E1, while not for CYP1A1, 1A2, 1B1 or 3A4. In the Chinese hamster (V79) cell line and its derivatives genetically engineered for the expression of human CYP1A1, 1A2, 1B1, 2E1 or 3A4 CBZ (2.5 ~ 40μM) did not induce micronucleus, while in human CYP2B6-expressing cells CBZ significantly induced micronucleus formation. In a human hepatoma C3A cell line, which endogenously expressed CYP2B6 twofold higher than in HepG2 cells, CBZ induced micronucleus potently, which was blocked by 1-aminobenzotriazole (inhibitor of CYPs) and ticlopidine (specific CYP2B6 inhibitor). In HepG2 cells CBZ did not induce micronucleus; however, pretreatment of the cells with CICTO (CYP2B6 inducer) led to micronucleus formation by CBZ, while rifampicin (CYP3A4 inducer) or PCB126 (CYP1A inducer) did not change the negative results. Immunofluorescent assay showed that CBZ selectively induced centromere-free micronucleus. Moreover, CBZ induced double-strand DNA breaks (γ-H2AX elevation, by Western blot) and PIG-A gene mutations (by flowcytometry) in C3A (threshold being 5μM, lower than its therapeutic serum concentrations, 17 ~ 51μM), with no effects in HepG2 cells. Clearly, CBZ may induce clastogenesis and gene mutations at its therapeutic concentrations, human CYP2B6 being a major activating enzyme.

ANALYSIS OF DOXORUBICIN-INDUCED MITOCHONDRIAL DNA DELETIONS IN HUMAN BLOOD LEUKOCYTES AND THP-1 CELL LINE BY PCR

Doxorubicin (DOX) is an antineoplastic drug with potent cardiotoxic activity due to selective accumulation and disruption of mitochondrial functioning in cardiomyocytes. Accumulating evidence indicates that DOX can also induce genotoxic side effects in other cells. The mutagenic effects of DOX in human peripheral blood leukocytes and THP-1 leukemia cells were analyzed using PCR. It was revealed that DOX could induce deletions of different sizes and loci of mitogenomes of normal human leukocytes and THP-1 leukemic cells.

Occurrence and mass loads of N-nitrosamines discharged from different anthropogenic activities in Desheng River, South China

N-nitrosamines are widespread in various bodies of water, which is of great concern due to their carcinogenic risks and harmful mutagenic effects. Livestock rearing, domestic, agricultural, and industrial wastewaters are the main sources of N-nitrosamines in environmental water. However, information on the amount of N-nitrosamines these different wastewaters contribute to environmental water is scarce. Here, we investigated eight N-nitrosamines and assessed their mass loadings in the Desheng River to quantify the contributions discharged from different anthropogenic activities. N-nitrosodimethylamine (NDMA) (< 1.6-18ng/L), N-nitrosomethylethylamine (NMEA) (< 2.2ng/L), N-nitrosodiethylamine (NDEA) (< 1.7-2.4ng/L), N-nitrosopyrrolidine (NPYR) (< 1.8-18ng/L), N-nitrosomorpholine (NMOR) (< 2.0-3.5ng/L), N-nitrosopiperidine (NPIP) (< 2.2-2.5ng/L), and N-nitrosodi-n-butylamine (NDBA) (< 3.3-16ng/L) were detected. NDMA and NDBA were the dominant compounds contributing 89% and 92% to the total N-nitrosamine concentrations. The mean cumulative concentrations of N-nitrosamines in the livestock rearing area (26 ± 11ng/L) and industrial area (24 ± 4.8ng/L) were higher than those in the residential area (16 ± 6.3ng/L) and farmland area (15 ± 5.1ng/L). The mean concentration of N-nitrosamines in the tributaries (22ng/L) was slightly higher than that in the mainstem (17ng/L), probably due to the dilution effect of the mainstem. However, the mass loading assessment based on the river's flow and water concentrations suggested the negligible mass emission of N-nitrosamines into the mainstem from tributaries, which could be due to the small water flow of tributaries. The average mass loads of N-nitrosamines discharged into the mainstem were ranked as the livestock rearing area (742.7g/d), industrial area (558.6g/d), farmland area (93.9g/d), and residential areas (83.2g/d). In the livestock rearing, residential, and industrial area, NDMA (60.9%, 53.6%, and 46.7%) and NDBA (34.6%, 33.3%, and 44.9%) contributed the most mass loads; NDMA (23.4%), NDEA (15.8%), NPYR (10.1%), NPIP (12.8%), and NDBA (37.8%) contributed almost all the mass loads in the farmland area. Photodegradation amounts of NDMA (0.65 ~ 5.25µg/(m3·day)), NDBA (0.37 ~ 0.91µg/(m3·day)), and NDEA (0 ~ 0.66µg/(m3·day)) were also calculated according to the mass loading. Quantifying the contribution of different anthropogenic activities to the river will provide important information for regional river water quality protection. Risk quotient (RQ) values showed the negligible ecological risks for fish, daphnid, and green algae.

Effect of colchicine mutagen on phenotype and genotype of Vigna unguiculata var. sesquipedalis the 7th generation

Abstract. Fathurrahman F, Mardaleni, Krisianto A. 2023. Title Effect of colchicine mutagen on phenotype and genotype of Vigna unguiculata var. Sesquipedalis the 7th generation. Biodiversitas 24: 1408-1416. The problem with long bean species is the low diversity of varieties, so obtaining them using chromosomal mutations was necessary. One of the ingredients used was colchicine. The aim of this study was to determine the effectiveness of the mutagen colchicine against mutations that occur in Vigna unguiculata var. sesquipedalis the 7th generation (renek long bean). The design used was a factorial Completely Randomized Design consisting of two factors. The first factor was four colchicine concentration levels: including without colchicine (the control) and colchicine concentration (0.01%, 0.05%, and 0.09%). The second factor was the soaking of the V. unguiculata var. sesquipedalis seeds, namely without soaking of seeds and soaking seeds (6, 12, 18, and 24 hours). Further phenotype analysis was tested statistically using the DMRT test at p &lt; 0.05, while genotypes were analyzed using karyotypes and statistical T-test at p &lt; 0.05. The results showed that treatment with 0.09% of colchicine and soaking for 24 hours was the best combination. Phenotype analysis showed increased growth with colchicine treatment: plant height increased by 20.59%, pod weight increased by 0.88%, the number of pods increased by 47.93%, pod length increased by 22.50%, and 100 seed weight increased by 15.91%. While Genotype analysis obtained a total of 11 karyotype chromosomes and 2n = 22 chromosomes. Chromosome karyotypes obtained two types, namely metacentric and telocentric. The arm length (p+q) in the 0.09% colchicine treatment sample and 24-hour soaking time was 1.77 µm longer than the control sample, which was 1.53 µm. It turns out that colchicine can increase the growth and changes in the structure of chromosomes so that a mutated V. unguiculata var. sesquipedalis species is obtained.

Chemical rules for optimization of chemical mutagenicity via matched molecular pairs analysis and machine learning methods

Chemical mutagenicity is a serious issue that needs to be addressed in early drug discovery. Over a long period of time, medicinal chemists have manually summarized a series of empirical rules for the optimization of chemical mutagenicity. However, given the rising amount of data, it is getting more difficult for medicinal chemists to identify more comprehensive chemical rules behind the biochemical data. Herein, we integrated a large Ames mutagenicity data set with 8576 compounds to derive mutagenicity transformation rules for reversing Ames mutagenicity via matched molecular pairs analysis. A well-trained consensus model with a reasonable applicability domain was constructed, which showed favorable performance in the external validation set with an accuracy of 0.815. The model was used to assess the generalizability and validity of these mutagenicity transformation rules. The results demonstrated that these rules were of great value and could provide inspiration for the structural modifications of compounds with potential mutagenic effects. We also found that the local chemical environment of the attachment points of rules was critical for successful transformation. To facilitate the use of these mutagenicity transformation rules, we integrated them into ADMETopt2 (http://lmmd.ecust.edu.cn/admetsar2/admetopt2/), a free web server for optimization of chemical ADMET properties. The above-mentioned approach would be extended to the optimization of other toxicity endpoints.Graphical

An Alternative Excipient from Vegetable Source for Oral Drug Dosage Forms to Regulate Drug Delivery

Abstract: Introduction: Tablet is the preferred drug dosage form. Cellulose fiber (Micro Crystalline Cellulose) is the major excipient used. For chronic diseases, frequent dosage is required resulting in cumulative excipient load and tachyphylaxis due to drug. We intent to invent excipients from vegetable sources to mitigate above challenges and reduce dosage as chronic sufferers (Diabetes mellitus) requires lifelong treatment. Aims and Objectives: To develop an excipient from Brassica oleracea and Vigna radiata sprouting which can regulate drug delivery, avoid excipient led toxicity and tachyphylaxis. Materials and Methods: Alkali and acid based depolymerization method was followed and cellulose fibers were studied for safety, physical, chemical and molecular parameters. With the developed cellulose fibers two drugs were formulated using Active Pharmaceutical Ingredient- Metformin and Miglitol. Efficacy was assayed using cell lines-Neuroblastoma, Kidney HK-2, L6 Myoblasts, 3T3-L1 Preadipocytes, INS-1 and HEPG 2 hepatocytes and compared with conventional micro crystalline cellulose- based formulations. Results: Characterization of developed excipients was done in comparison with conventional cellulose, invented excipients had long fibers, higher bulk density, flow, even particle size compared to conventional cellulose. Dissolution and disintegration of Metformin from Brassica oleracea fiber was slow and Miglitol showed quick release from Vigna radiata compared to conventional excipient. Therapeutic effect of both drugs from developed excipients was higher compared to conventional excipient-based drug by cell culture assay. Both developed excipients did not show mutagenic effect. Conclusion: Brassica oleracea fiber slows release of metformin; may reduce drug dosage, tachyphylaxis, release of Miglitol from Vigna radiata was rapid, may compliment metformin therapy. Keywords: Herbal excipients, Cellulose fibers, Microcrystalline cellulose, Tachyphylaxis, Vegetable source excipient, Brassica oleracea, Vigna radiata, Metformin, Miglitol.

A novel role for Mms2 in the control of spontaneous mutagenesis and Pol3 abundance

Mms2 is a ubiquitin E2-variant protein with a very well-documented function in the tolerance pathway that protects both human and yeast cells from the lethal and mutagenic effects of DNA damage. Interestingly, a high expression level of human MMS2 is associated with poor survival prognosis in different cancer diseases. Here we have analyzed the physiological effects of Mms2 overproduction in yeast cells. We show that an increased level of this protein causes a spontaneous mutator effect independent of Ubc13, a cognate partner of Mms2 in the PCNA-polyubiquitinating complex responsible for the template switch. Instead, this new promutagenic role of Mms2 requires Ubc4 (E2) and two ubiquitin ligases of HECT and RING families, Rsp5 and Not4, respectively. We have established that the promutagenic activity of Mms2 is dependent on the activities of error-prone DNA polymerase ζ and Rev1. Additionally, it requires the ubiquitination of K164 in PCNA which facilitates recruitment of these translesion polymerases to the replication complex. Importantly, we have established also that the cellular abundance of Mms2 influences the cellular level of Pol3, the catalytic subunit of replicative DNA polymerase δ. Lack of Mms2 increases the Pol3 abundance, whereas in response to Mms2 overproduction the Pol3 level decreases. We hypothesize that increased levels of spontaneous mutagenesis may result from the Mms2-induced reduction in Pol3 accumulation leading to increased participation of error-prone polymerase ζ in the replication complex

Possible Side Effects of Polyphenols and Their Interactions with Medicines

Polyphenols are an important component of plant-derived food with a wide spectrum of beneficial effects on human health. For many years, they have aroused great interest, especially due to their antioxidant properties, which are used in the prevention and treatment of many diseases. Unfortunately, as with any chemical substance, depending on the conditions, dose, and interactions with the environment, it is possible for polyphenols to also exert harmful effects. This review presents a comprehensive current state of the knowledge on the negative impact of polyphenols on human health, describing the possible side effects of polyphenol intake, especially in the form of supplements. The review begins with a brief overview of the physiological role of polyphenols and their potential use in disease prevention, followed by the harmful effects of polyphenols which are exerted in particular situations. The individual chapters discuss the consequences of polyphenols' ability to block iron uptake, which in some subpopulations can be harmful, as well as the possible inhibition of digestive enzymes, inhibition of intestinal microbiota, interactions of polyphenolic compounds with drugs, and impact on hormonal balance. Finally, the prooxidative activity of polyphenols as well as their mutagenic, carcinogenic, and genotoxic effects are presented. According to the authors, there is a need to raise public awareness about the possible side effects of polyphenols supplementation, especially in the case of vulnerable subpopulations.

Plant-ZnO nanoparticles interaction: An approach to improve guinea grass (Panicum maximum) productivity and evaluation of the impacts of its ingestion by freshwater teleost fish

We aimed to evaluate the possible effects of the application of zinc oxide nanoparticles [ZnO NPs; 68.96 ± 33.71 nm; at 100 and 500 mg/kg in a soil mixture of the Typic Dystrophic Red Latosol type and sand (2:1 ratio)] in the cultivation of Panicum maximum (until 125 days), using different biomarkers in addition to evaluating the uptake of Zn by the plants. Furthermore, we assessed the possible transfer of ZnO NPs from P. maximum leaves to zebrafish and their potential. Plants cultivated in substrates with ZnO NPs at 500 mg/kg showed reduced germination rate and growth. However, at 100 mg/kg, plants showed higher biomass and productivity, associated with higher Zn uptake, without inducing oxidative and nitrosative stress. Zinc content in zebrafish was not associated with ingesting leaves of P. maximum cultivated in substrate containing ZnCl2 or ZnO NPs or with genotoxic, mutagenic, and biochemical effects. In conclusion, ZnO NPs (at 100 mg/kg) are promising in the cultivation of P. maximum, and their ingestion by zebrafish did not cause changes in the evaluated biomarkers. However, we recommend that studies with other animal models be conducted to comprehensively assess the ecotoxicological hazard associated with applying ZnO NPs in soil.

Mutagenic effects of colchicine on the morphology and yield of three tomato (Solanum lycopersicum L.) accessions

The mutagenic effect of Colchicine on the morphology and yield of tomato was investigated. Seeds of three tomato accessions (NG/MR/May/09/005- SouthWest, NG/SA/07/10/002- NorthEast and NG/CHU/Jun/0201-SouthEast) were presoaked in four different concentrations of Colchicine (0.1mM, 0.3mM, 0.5mM, 1.0mM) and 0.0mM as control. The domestic demand for tomato extremely exceeds the supply with over 2-3 million metric tons annually thereby involving Nigeria into importing about 300,000 metric tonnes worth over $360 million dollar yearly. The experiment was laid in Randomized Complete Block Design in five replications. The morphological parameters used to characterize the mutants were plant height, number of leaves/plant, leaf length, number of branches, number of days to first flowering, fruit weight, germination percentage and number of fruit/plant. The results revealed significant difference (p&lt;0.05) in some of the morphological traits assessed when compared with the controls, except in the number of branches and plant height, where the effect of the mutagen was not important (p&gt;0.05). The morphological and yield parameters of the southwest and northeast accessions of tomato as observed in this study, improved with decreasing concentration of Colchicine, while the southeast improved with increase in the concentration of Colchicine. It is thus recommended that, to improve growth and yield parameters in tomatoes, 0.1mM concentration should be employed to improve Southwest and Northeast tomato accessions, while 0.5mM or 1.0mM concentrations should be used in the Southeast tomato accessions.

Evaluation of in vitro and in vivo Anti-neuroinflammatory and Genotoxic Activities of the Alkaloid Tryptophol-5-O-β-D-glucopyranoside from Ocotea minarum

Ocotea minarum (Nees & Mart.) Mez is a tree belonging to the Lauraceae family and found in the Brazilian Cerrado ecosystem. Although the chemical composition of this species has already been described, little is known about the biological activities of one of the constituents of its fruits-the alkaloid tryptophol-5-O-β-D-glucopyranoside. In the present study, we assessed the anti-neuroinflammatory, mutagenic and recombinogenic properties of this indole alkaloid. Cytotoxicity and anti-inflammatory activities were performed using a model of LPS-stimulated microglia BV-2. Mutation detection and somatic recombination were performed in Drosophila melanogaster wing cells. The results showed that tryptophol-5-O-β-D-glucopyranoside was not cytotoxic to BV-2 cells at the concentrations tested. The results also showed that this alkaloid inhibited by 75% the inflammatory response induced by LPS at the concentration of 189 μM with IC50 = 12.07±0.35 μM. The analysis of the MH offspring showed that different concentrations of the alkaloid did not induce statistically significant increases in the frequencies of mutant spots when compared to those observed in the negative control. With these results, we can conclude that tryptophol-5-O-β-D-glucopyranoside presents therapeutic potential for the treatment of neurodegenerative diseases with no mutagenic effects.

Characterization and Selection by Optical Absorption and Emission Spectrophotometry of a Series of Red Dyes Capable of Destroying Far UV Rays by Absorption

The far ultraviolet rays are harmful to human health, particularly for their mutagenic effects; it can cause skin cancer, cataracts, photochemical pollution. In the future, chemists plan to use it as weapons for the destruction of objects. Therefore, we should meet this future challenge by scientific means in order to snuff out its far-ultraviolet rays. In this paper, we’ve intend to carry out a deep spectral study on a series of red dyes such as: beet red; congo red; methyl red; neutral red; phenol red and carminic acid, to find out which are able to damage far ultraviolet rays by absorption. The experimental results have been carried out in our laboratory; it has shown that certain red pigments have an ability to absorb light in the far ultraviolet range due to their chemical structures. Therefore, they are able to dodging far ultraviolet rays. Moreover, the spectral analyzes by the emission of the series of red dyes studied, have showed that these red dyes emit beyond 600 nm.

Application of Sulfate-reducing Bacteria in Bioremediation from Heavy Metals and Metalloids (Review)

Pollution of the environment with heavy metals, metalloids and radionuclides is a global problem that seriously affects the state of the biosphere. In particular, chromium compounds have a toxic, mutagenic and carcinogenic effect. The main principle of purification of anthropogenic and natural ecosystems from chromates is the reduction of Cr(VI) to Cr(III), the salts of which are significantly less toxic and insoluble. However, currently used electrochemical and ion-exchange cleaning methods are quite expensive and require the use of special reagents. At the same time, sulfate-reducing bacteria (SRB) are of particular interest for bioremediation of this kind, since many of them are very resistant to high concentrations of heavy metals and are able to effectively reduce them in the presence of hydrogen as an electron donor. The review summarizes known data on the interaction of heavy metals, metalloids and radionuclides with SRB. The features of the metabolism of these microorganisms, leading to intracellular accumulation of heavy metals and metalloids, are considered. Complex and finely regulated enzymatic mechanisms for the reduction of toxic metals (using various cytochromes, hydrogenases, oxidoreductases, highly specific metal reductases, and thioredoxin/thioredoxin-reductase systems), as well as the possibility of using immobilized cells and biofilms of SRB in the effective bioremediation of natural waters, soils, and industrial effluents, are described.