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Enaminon türevleriyle aromatik aminlerin diazonyum tuzlarının reaksiyonundan azo boyaları (AD-1, AD-2) sentezlendi. Sentezlenen yeni azo boyanın (AD-2) kimyasal yapısı, elementel analiz ve diğer spektral tekniklerle (FTIR, 1H NMR ve 13C NMR) karakterize edildi. Azo boyaları endüstride sıklıkla kullanılmakta ve özellikle su kaynakları için büyük tehlike oluşturmaktadır. Bu bakımdan azo boyalar tarımsal uygulamalarda birçok ürünü dolaylı olarak tehdit etmektedir. Bu çalışmada, endüstriyel uygulamalarda kullanılabilecek potansiyel azo boyaların (AD-1, AD-2) sitotoksik ve genotoksik etkileri, Allium test sistemi kullanılarak beş farklı konsantrasyonda (6.25, 12.5, 25, 50 ve 100 µM) belirlendi. Sitogenetik analizler sonucunda, her iki azo boyanın da A. cepa hücrelerinin bölünme sayısını önemli ölçüde azalttığı ve bölünen hücrelerde kromozomal anormalliklere neden olduğu belirlendi. Sonuç olarak, bu araştırmada, endüstride potansiyel olarak kullanılabilecek azo boyaların (AD-1, AD-2) canlı yapılarda genotoksik ve sitotoksik etkilere neden olduğu vurgulanmaktadır., Azo dyes (AD-1, AD-2) were synthesized from the reaction diazonium salts of the aromatic amines salt with the enaminone derivative. The chemical structure of the synthesized novel azo dye (AD-2) was characterized by elemental analysis and other spectral techniques (FTIR, 1H NMR and 13C NMR). Azo dyes are used frequently in the industry and pose a great danger especially for water resources. In this respect, azo dyes threaten many products indirectly in agricultural applications. In this study, the cytotoxic and genotoxic effects of potential azo dyes (AD-1, AD-2) that can be used in industrial applications were determined using Allium test system in five different concentrations (6.25, 12.5, 25, 50, and 100 µM). As a result of the cytogenetic analyzes, it was determined that both azo dyes significantly reduced the number of divisions of A. cepa cells and caused chromosomal abnormalities in dividing cells. As a result, in this research, it is emphasized that the azo dyes (AD-1, AD-2), which are potentially used in the industry, cause genotoxic and cytotoxic effects in the living structures.

In the present study, we investigated cytogenetic and oxidative [total antioxidant capacity (TAC), total oxidant status (TOS)] effects of methanol and water extracts of Cladonia chlorophaea (Flörke ex Sommerf.) Sprengel, Dermatocarpon miniatum (L.) W.Mann and Parmelia saxatilis (L.) Ach. on cultured human lymphocytes. In addition, different phenolic compounds in the extracts were quantified by high performance liquid chromatography (HPLC) analysis. As a result of HPLC analysis, methanol extracts of all lichen species tested had higher phenolic compounds. Likewise, methanol extracts of each lichen increased TAC levels in lymphocytes more than water extracts. The TOS levels of the cells treated with different concentrations (1–100 mg/L) of the extracts decreased due to the increasing concentration of the extracts. Genotoxicity experiments revealed that the tested lichen extracts did not significantly increase (p > 0.05) the level of genotoxicity on human peripheral lymphocyte culture compared to the negative control group. The results showed that C. chlorophaea, D. miniatum and P. saxatilis lichens, which were found to be a rich source of phenolic compounds, might be of interest in the pharmaceutical and food industries.

Aims: In this study, we determined that whether the liquid extracts of the above-ground parts of Vaccinium myrtillus L. and Rubus idaeus L. have antimutagenic effects against mitomycin C in human peripheral lymphocytes, chromosome aberration (CA), micronucleus (MN) and mitotic index (MI) tests. Methodology: Blood samples of the negative control group (Group I) were allowed to react in a cell culture medium without any treatment, while positive control group (Group II) was allowed to interact in a cell culture medium supplemented with mitomycin-C (MMC) at a dose of 0.3 μL /mL for each chromosome medium. Blood samples of the other groups were allowed to react for 24 hours with 0.3 μL /mL MMC and V. myrtillus L. (Group III, IV, V and VI), and R. idaeus L. (VII, VIII, IX and X) extracts in 0.2 μL /mL, 0.4 μL /mL, 0.8 μL /mL and 1.6 μL /mL doses for each of cell cultures. At the end of the incubation period, culture cells were evaluated by chromosomal aberrations, mitotic, micronucleus and nuclear division index tests. Results: Compared with Group II, it was determined that mitotic, nuclear division and nuclear cytotoxic cleavage indices were increased when chromosome aberrations and micronucleus indexes were decreased in extract groups. When we compared to extract groups and group II, we observed that chromosome aberrations and micronucleus index decreased in extract groups, while mitotic, nuclear division and nuclear cytotoxic cleavage indices were increased. Conclusion: It was concluded that aqueous extracts of V. myrtillus L. and Rubus idaeus L. had significantly antimutagenic effects on the human peripheral lymphocyte cells at the working doses.

Fulvic acid (FA), a humic substance, has several nutraceutical properties, including anti-inflammation, antimicrobial, and immune regulation abilities. However, systematic safety assessment remains insufficient. In the present study, a battery of toxicological studies was conducted per internationally accepted standards to investigate the genotoxicity and repeated-dose oral toxicity of FA. Sprague-Dawley (SD) rats or ICR mice were used. Compared to the control group, there were no significant changes (all p > 0.05 ) in all FA treatment groups in the bacterial reverse mutation test, in vitro mammalian chromosome aberration test, in vivo sperm shape abnormality assay, and in vivo mouse micronucleus assay. The acute toxicity test showed that no mortality or toxic effect was observed following oral administration of the maximum dose of 5,000 mg/kg BW/day to mice or rats. A 60-day subchronic study was conducted at 0 (control), 200, 1,000, and 5,000 mg/kg/day. Compared to the control group, there were no significant changes (all p > 0.05 ) in the body weights, feed consumption, clinical signs, hematology, clinical chemistry, organ weights, or histopathology examinations. In conclusion, the no-observed-adverse-effect-level (NOAEL) of FA supplementation from the 60-day study was determined to be 5,000 mg/kg body weight/day, the highest dose tested. Our findings suggest that the oral administration of FA may have higher safety.

This study investigated the protective effective of Sida acuta leaf extracts against the genotoxic effect of lead nitrate, a toxic heavy metal that easily permeate the ecosystem. The genotoxic and anti-genotoxic effects of the aqueous extract of S. acuta on onion cells (Allium cepa L.) was evaluated using the Allium cepa L. assay. Onion bulbs were exposed to 0.25 – 2.5 mg.mL-1 concentrations of the plant extract for analyses of induction of cytogenetic damage. There was observeda concentration-dependent decrease in mitotic index of the A. cepa roots cells compared to the negative control. Lead nitrate significantly induced chromosomal aberration in A. cepa root cells. This effect, however, was significantly ameliorated by the S. acuta leaf extract. This effect was demonstrated by the lower frequency of chromosome aberrations in lead nitrate treated root cells after exposure to the extract. Furthermore, the extract restricted the extent of lead-induced cytological aberrations in A. cepa. The findings in this study suggested the mitodepressive, antiproliferative and anti-genotoxic potentials of the extract.

Introduction: Acute myeloid leukaemia (AML) is a highly malignant clonal hematopoietic disease caused by both inherited and acquired genetic alterations (Song et al, 1999). Current AML classification and prognostic systems incorporate genetic information but are limited to known abnormalities that have previously been identified with the use of cytogenetics, array comparative genomic hybridization (CGH), gene-expression profiling, and the resequencing of candidate genes. At diagnosis, most patients with AML harbour at least 1 chromosome aberration in their marrow blasts. Numerous recurrent structural and numeric cytogenetic aberrations have been identified and many of them not only are diagnostic markers for specific AML subtypes but also constitute independent prognostic factors for attainment of complete remission (CR), relapse risk, and overall survival (OS) (Mro´zeket al, 2007). With the targeted cytogenetic therapy, 30% of the patients achieve long-term cure. At University Teaching Hospital(UTH) however, the current diagnostic approach of acute leukaemia involves mainly cytomorphology and occasional flow cytometry. The cytomorphological blast characterization is not enough to provide a critical determination of prognosis and developing a treatment plan. Most of the AML patients at the UTH die within few months after diagnosis despite being put on chemotherapy. Cytogenetic analysis is not done despite the cytogenetic abnormalities being the major predictors of favourable, intermediate or adverse prognosis. Aim: To characterize acute myeloid leukaemia (AML) according to WHO 2008 revised classification in patients at the University Teaching Hospital. Design and Methods: This was a descriptive cross-sectional study conducted to characterize acute myeloid leukaemia (AML) according to WHO 2008 revised classification in patients at the UTH. Patients with AML were simultaneously analyzed for the presence of 4 genetic abnormalities, PML/RARα for t(15;17), AML1/ETO for t(8;21), CBFβ/MYH11 for inv(16)/t(16;16) and rearrangements of the MLL gene for 11q23 abnormalities. AML was classified using the new World Health Organization (WHO) classification for haematologic malignancies. The techniques used were standardized according to the recommendations of the European BIOMED-1 Concerted Action. Results: The overall frequency of leukemia displaying one of the four recurrent cytogenetic translocations were 13 cases (46.5%) of which PML/RARα transcript was present in six(6) patients (21.4%) (3 were bcr1, 1 bcr2 and 2 bcr3). The AML1/ETO fusion transcript was detected in only one(1) case (3.6%) with M2 morphology, but other cases with M2 morphology were negative. CBFβ/MYH11 transcript was present in 2 cases (7.1%) and some of them displaying M4Eo morphology. Finally, 4 cases (14.3%) showed rearrangements of the MLL gene. By contrast, the frequency of AML not otherwise characterized which was 15 cases (53.6%) increased with age (13% for 6-35years age group, 20% for 36-65years age group and 67% for above 66years age group). Our results differ from those reported from the United States and North/Central Europe, particularly regarding the incidence of t(15;17) and t(8;21) translocations. In Zambia the frequency of t(15;17) is higher while that of t(8;21) is lower. This supports the view that geographic variations in tumor-associated aberrations in hematologic malignancies exist. Conclusions: Our study showed that chromosomal alteration PML/RAR t(15,17) which was 21.4% ,was the commonest, whereas AML1/ETO t(8,21) which was 3.6%,was the least common among patients presenting at UTH, Lusaka, Zambia. Our study showed that chromosomal aberration detected in our patients make them less responsive to cytotoxic drugs. The use of molecular technique at point of diagnosis would assist in identifying AML with better prognosis by administering appropriate treatment. The results support the existence of chromosomal abnormalities of AML in our Zambian patients. Awareness of these chromosomal abnormalities and morphology could contribute to the design of cost-effective screening strategies, adapted by our National Health systems according to the prevalence of locally detected genetic aberrations. Acquired genetic alterations such as balanced and unbalanced chromosome aberrations and submicroscopic gene mutations and changes in gene expression strongly affect pre-treatment features and prognosis of patients with acute myeloid leukemia (AML).

Because zinc sulfate (ZnSO4) is widely used in many fields such as biomedicine, electronics, and chemistry, it is important to evaluate its toxic effects. In this study, the cyto-genotoxic effects of ZnSO4 on meristematic cells in the root tip of Allium cepa L. were investigated. After calculating the effective concentration (EC50 = 70 ppm) of ZnSO4, A. cepa root tip cells were suspended for 24, 48, 72, and 96 h in solutions of 35 ppm (EC50/2), 70 ppm (EC50), and 140 ppm (EC50 × 2) concentrations. Using the counts of dividing cells, the mitotic index (MI) was calculated. Chromosome aberration index (CAI) was determined from percentages of abnormal cells. When the obtained data were statistically evaluated, it was determined that all application concentrations caused a significant decrease in MI and an increase in CAI compared to the control group (distilled water). It was concluded that increased ZnSO4 dose concentrations and exposure times caused cytotoxicity and genotoxicity in the root cells of A. cepa L.

Nowdays the problem of fires is becoming more widespread and global in scale. According to statistics published by the Ukrainian Research Institute of Civil Protection obtained as a result of analysis of the fire registration cards of the SES of Ukraine – for 11 months of 2019 the number of fires in Ukraine increased by 23.1% compared to the same period last year. The most common extinguishing agent being used by fire and rescue units today is а foam. The main component of different foaming agents are surfactants. Their excessive emission into the environment leads to pollution of the surrounding areas. The constant increasing of the land areas affected by the effects of firefighting influence both the state of the environment in the region as a whole and the level of soil fertility. Microbiological indicators and the content of harmful substances in crops are increasing and thus the negative impact on public health grows. The analysis of microbiological monitoring methods with the aim of the contaminated solutions foam makers impact on the nearby territories’ soils estimation has been carried out. The pros and cons of modern physical and chemical methods of soils quality estimation have been defined. The necessity of microbiological methods usage which allow to get full and sufficient information not only about the pollution volume, but also to rate the results of such pollution has been justified. It is determined that in order to obtain the most complete and objective information about the microbiological condition of soils contaminated with foaming agents for fire extinguishing, a complex of bioindication methods should be used. It should include a growth test and a chromosome aberration test, with the use of test organisms that are most sensitive to the chemical composition of the test solution for firefighting.

Titanium dioxide nanoparticles (TiO2 NPs, size 2 NPs can cause inflammation, cytotoxicity, genotoxicity and cell apoptosis. In this article, we have reviewed the recent literature on the potential of TiO2 NPs to cause genotoxicity and summarized the results of two standard genotoxicity assays, the comet and micronucleus (MN) assays. Analysis of these peer-reviewed publications shows that the comet assay is the most common genotoxicity test, followed by MN, Ames, and chromosome aberration tests. These assays have reported positive as well as negative results, although there is inconsistency in some results that need to be confirmed further by well-designed experiments. We also discuss the possible mechanisms of TiO2 NP genotoxicity and point out areas that warrant further research.

Background Benzene, an important component of organic solvents, is commonly used in industry. Meanwhile, benzene is a human carcinogen leading to leukemia. Although the links between benzene and various types of genetic damage indicators have been evaluated in several studies, but their results remain inconsistent. So we conducted a meta-analysis, and to explore the influence of low concentration benzene exposure on workers’ genetic damage indicators using 3.25 mg/m3 as the boundary value, in order to provide a basis for improved prevention and control of the harm from benzene exposure to the occupational population. Methods We conducted a search of five databases, including Pub Med, Web of Science, China National Knowledge Infrastructure (CNKI), Wan Fang Data and Chongqing VIP, to identify relevant articles up to December 25, 2018. Two researchers independently extracted and evaluated the data according to the inclusion and exclusion criteria of the literature. The imported articles were managed by Endnote X7, and the data were extracted and sorted by Excel 2013. We utilized Stata 12.0 software to perform the meta-analysis in the present study. Results A total of 68 eligible articles were finally included for the synthetic analyses. The meta-analysis results showed that occupational benzene exposure led to significantly increased Micronucleus (MN) frequency, Sister chromatid exchange (SCE) frequency, Chromosome aberration (CA) frequency, Olive Tail moment (OTM), Tail moment (TM), Tail length (TL), and Tail DNA% (T DNA%) compared to the control group (P P Conclusions Occupational benzene exposure can affect multiple genetic damage indicators. Even at an exposure concentration lower than 3.25 mg/m3, benzene exposure has genotoxicity. These data provide an important scientific basis for the further revision of occupational disease prevention strategies. At the same time, increased attention should be focused on the health monitoring of the occupational population exposed to benzene, and health management should be strengthened to improve the health of the occupational population.

Introduction: Currently fetal nuchal translucency (NT) ≥3.5 mm is an indication for invasive testing often followed by chromosomal microarray. The aim of this study was to assess the risks for chromosomal aberrations in fetuses with an NT 3.0-3.4 mm, to determine whether invasive prenatal testing would be relevant in these cases and to assess the residual risks in fetuses with normal non-invasive prenatal test (NIPT) results. Material and methods: A retrospective study and meta-analysis of literature cases with NT between 3.0 and 3.4 mm and 2 cohorts of pregnant women referred for invasive testing and chromosomal microarray was performed: Rotterdam region (with a risk >1:200 and NT between 3.0 and 3.4 mm) tested in the period July 2012 to June 2019 and Central Denmark region (with a risk >1:300 and NT between 3.0 and 3.4 mm) tested between September 2015 and December 2018. Results: A total of 522 fetuses were referred for invasive testing and chromosomal microarray. Meta-analysis indicated that in 1:7.4 (13.5% [95% CI 8.2%-21.5%]) fetuses a chromosomal aberration was diagnosed. Of these aberrant cases, 47/68 (69%) involved trisomy 21, 18, and 13 and would potentially be detected by all NIPT approaches. The residual risk for missing a (sub)microscopic chromosome aberration depends on the NIPT approach and is highest if NIPT was performed only for common trisomies–1:21 (4.8% [95% CI 3.2%-7.3%]). However, it may be substantially lowered if a genome-wide 10-Mb resolution NIPT test was offered (~1:464). Conclusions: Based on these data, we suggest that the NT cut-off for invasive testing could be 3.0 mm (instead of 3.5 mm) because of the high risk of 1:7.4 for a chromosomal aberration. If women were offered NIPT first, there would be a significant diagnostic delay because all abnormal NIPT results need to be confirmed by diagnostic testing. If the woman had already received a normal NIPT result, the residual risk of 1:21 to 1:464 for chromosome aberrations other than common trisomies, dependent on the NIPT approach, should be raised. If a pregnant woman declines invasive testing, but still wants a test with a broader coverage of clinically significant conditions then the genome-wide >10-Mb resolution NIPT test, which detects most aberrations, could be proposed.

Detection of translocations in subtelomeric regions of chromosomes is a serious diagnostic problem, because they are difficult to determine by conventional cytogenetics with G banding. The aim of this work was the development of the technology of DNA probe synthesis for unique sequences of subtelomeric chromosome regions based on long-range PCR using the clinical case of determining the parental origin of unbalanced translocation between chromosomes 5 and 8. The unbalanced translocation der(5)t(5;8)(р15.33;q24.22) in a proband with physical, motor, intellectual, and speech development delay and in his sibling with speech and intellectual development delay as well, which was previously identified by array comparative genomic hybridization (aCGH), was confirmed by FISH. A balanced translocation 46,XX,t(5;8)(p15.33;q24.22) was detected in the mother’s karyotype using the created locus-specific DNA probe. This chromosome aberration was not detected by G banding of metaphase chromosomes. The father’s karyotype was normal according to FISH results. The method presented here makes it possible to create locus-specific DNA probes in a molecular cytogenetic laboratory using long-range PCR for the rapid diagnosis of cryptic chromosomal rearrangements.

Background: This investigation was designed to evaluate the chemical composition, antioxidant, anti-inflammatory, genotoxicity, and antimicrobial activities of Curcuma caesia Roxb rhizome essential oil. Methods: Gas Chromatography/Mass Spectroscopy (GC/MS) analysis was performed to determine the chemical composition, standard antioxidative test DPPH assay, reducing power assay, in vitro antiinflammatory activity (egg albumin denaturation, protease inhibitory assay) by using standard methods. Similarly, antimicrobial activity was tested using the disc diffusion method, minimum inhibitory concentration ability (MIC); while to test genotoxicity, Allium cepa assay was used. Results: GC/MS analysis revealed eucalyptol (28.55%), epicurzerenone (19.62%), and camphor (21.73%) as the major components of C. caesia rhizome essential oil. Potent antioxidant (IC50= 48.08±0.003 μg/mL), anti-inflammatory (IC50= 121.7±0.0013 μg/mL), and antimicrobial activities of the essential oil were recorded better than the standard drugs Fluconazole for fungus and Ciprofloxacin for bacteria. The essential oil also possessed a strong antibacterial effect against two tested bacterial strains B. subtilis and B. cereus with 7.5 μg/mL MIC value, while for fungal strains the essential oil was most effective against S. cereviaceae with an MIC value of 2.5 μg/mL. All the data were recorded in triplicates. Allium cepa assay revealed minor genotoxicity with mitotic index, MI= 27.70%; chromosome aberration, A= 1.1% of C. caesia rhizome essential oil. Conclusion: C. caesia rhizome essential oil possesses potent antioxidant, anti-inflammatory, and antimicrobial properties with negligible genotoxicity. Hence, the present study is highly significant for the utilization of rhizome of C. caesia, a high-value ethnopharmacological plant for advanced R & D and commercial application.

OBJECTIVES To determine the detection rates of all types of chromosome aberrations and the residual risk for postnatal diagnosis of an atypical chromosome aberration depending on the strategy for further investigation with either noninvasive prenatal testing (NIPT) or invasive testing in pregnancies with increased risk following combined first-trimester screening (cFTS). METHODS A review of all pregnancies examined with cFTS during 2010 to 2017. RESULTS The cohort consisted of 129 493 pregnancies. There were 852 (0.7%) clinically significant chromosome aberrations, including aberrations detected later on or after birth. A total of 12% were atypical chromosome aberrations. Considering that 40% were detected due to a miscarriage/intrauterine fetal death or a malformation on ultrasound there is a 0.05% (1:2000) background risk of a postnatal diagnosis of a liveborn child with an atypical chromosome aberration if no further invasive test is performed during pregnancy. If all women with an increased risk (≥1:200) had an invasive test and NIPT was performed up to a risk of 1:1000, 95% of common trisomies/sex chromosome aberrations and 55% of atypical aberrations would be detected. CONCLUSIONS If NIPT was offered to all women with an increased risk following cFTS it would imply that three times as many children would be born with an atypical chromosome aberration.

Background/aim Aspartame (APM, L-aspartyl-L-phenylalanine methylester) is a low-calorie, nonsaccharide artificial sweetener widely used in foods and beverages. When metabolized by the body, APM is broken down into aspartic acid, phenylalanine amino acids, and a third substance, methanol. Since the amino acid phenylalanine serves as a neurotransmitter building block affecting the brain, and methanol is converted into toxic formaldehyde, APM has deleterious effects on the body and brain. Thus, its safety and, toxicity have been the subjects of concern ever since it was first discovered. Although many studies have been performed on it, due to the presence of conflicting data in the literature, there are still numerous question marks concerning APM.Therefore, the safety of aspartame was tested using in vitro methods. Materials and methods We aimed to evaluate the in vitro cytotoxic effects by using 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase release tests, genotoxic damage potential by using chromosome aberration (CA) assay, and antioxidant/oxidant activity by using total antioxidant capacity (TAC) and total oxidative stress (TOS) analysis in primary human whole blood cell cultures. Results The results of the MTT test showed that APM led to significant decreases in cell viability in a clear concentration-dependent manner. Moreover, an increase in CA frequency was found in the cells treated with APM. However, APM treatments did not cause any significant changes in TAC and TOS levels in whole blood cultures. Conclusion Overall, the obtained results showed that APM had genotoxicity potential and a concentration-dependent cytotoxic activity in human blood cells.

The aim of this study was to investigate the response of chromosomes in typical human and plant cells under applied low-frequency magnetic fields at low and high intensities. Neuronal-like cells and roots of

We performed general toxicity studies of Gryllus bimaculatus (two-spotted cricket) glycosaminoglycan (GbG), including a single, 4-week repeated oral dose toxicity test in ICR mice, and short-term genotoxicity tests. The mutagenic potential of the purified GbG was non-genotoxic when it was evaluated using short-term genotoxicity tests, namely Ames, chromosome aberration (CA), and micronuclei (MN) tests. In Salmonella typhimurium and Escherichia coli assays, GbG did not produce any mutagenic response in the absence or presence of S9 mix with five bacterial strains (TA98, TA100, TA1535, TA1537, and WP2uvrA). Chromosome aberration test showed that GbG had no significant effect on Chinese hamster ovary (CHO) cells. In mouse micronuclei tests after twice oral treatments per day for two days, no significant alteration in the occurrence of micronucleated polychromatic erythrocytes was observed in ICR male mice intraperitoneally administered with GbG at doses of 15.63, 31.25, or 62.50 mg/kg. These results indicate that GbG has no mutagenic potential in these in vitro and in vivo systems. After GbG was orally administered at doses of 20, 40, 80, and 160 mg/kg for a single oral dose toxicity study and at 0, 40, 80, and 160 mg/kg bw/day for 4-week oral dose toxicity study, there were no observed clinical signs or deaths related to treatment in any group tested. Therefore, the approximate lethal oral dose of GbG was considered to be higher than 160 mg/kg in mice. Throughout the administration period, no significant changes in diet consumption, ophthalmologic findings, organ weight, clinical pathology (hematology, clinical chemistry, coagulation, and urinalysis), or gross pathology were detected. Microscopic examination did not identify any treatment-related histopathologic changes in organs of GbG-treated mice in the high dose group. These results indicate that the no-observed adverse effect level (NOAEL) of GbG is higher than 160 mg/kg bw/day in mice.

Glutaminase (glutamine aminohydrolase EC 3.5.1.2) is used in the production of food ingredients rich in l‐glutamic acid that are added to finished foods for the purpose of enhancing or improving the savory flavor profile of food. The glutaminase enzyme preparation evaluated in these studies, designated as Sumizyme GT hereafter, is obtained by fermentation of Aspergillus niger strain GT147. The safety of Sumizyme GT was evaluated in a series of standard toxicological studies, including a 90‐day oral toxicity study in rats, an in vitro bacterial reverse mutation assay, an in vitro mammalian chromosome aberration test, and an in vivo alkaline Comet assay. Sumizyme GT was not mutagenic or genotoxic, and administration of the enzyme by gavage at doses up to 2,570 mg total organic solids (TOS)/kg body weight (bw) per day for 90 days was without any systemic toxicity. The no‐observed‐adverse‐effect level was concluded to be 2,570 mg TOS/kg bw per day, the highest dose tested. Considering that A. niger has an established history of safe use in the food industry and its safety in the production of food ingredients and food enzymes is well documented, the results of these studies provide further support of the safety of glutaminase from A. niger when used in food production., Glutaminase from nongenetically modified Aspergillus niger was evaluated in a series of toxicological tests. The results of these studies demonstrate that glutaminase is nonmutagenic and nongenotoxic, and provide further support of the safety of glutaminase from A. niger when used in food production.

第36回宇宙環境利用シンポジウム (2022年1月18日-19日. オンライン開催), Space Utilization Research (January 18-19, 2022. Online Meeting), 資料番号: SA6000168016, F-04

The aim of present study, to evaluate the genotoxic potential of 1-(4-(3,3-dimethyl-1,6-dioxo-2,3,4,6,11,13-hexahydro-1H-indazolo[1,2b] phthalazine-13yl) phenyl)-2-phenylazetidine-3-yl-acetate which was synthesised assuming that it may be a pharmaceutical raw material and found to inhibit human carbonic anhydrase I, II isozymes. To determine the genotoxic potential of this phthalazine substituted ?-lactam compound, chromosomal aberration (CA) and micronucleus (MN) tests were implemented in human peripheral blood lymphocytes. In these tests, lymphocyte cultures were treated with four concentrations (30, 15, 7.5, 3.75 ?g/mL) of test compound and simultaneously with negative control (sterile distilled water), solvent control (DMSO) positive control (MMC). According to our results, CA frequencies were significantly increased in two high applied concentrations (30, 15 ?g/mL) compared with negative and solvent control. MN frequencies were significantly increased in three applied concentrations (30, 15, 7.5 ?g/ mL) except lowest concentration (3.75 ?g/mL) compared with solvent control. Mitotic indices were also affected by treatment with test compound. The obtained results provide evidence to demonstrate that new phthalazine substituted ?-lactam derivative can exert genotoxic and cytotoxic effects in peripheral human lymphocytes especially at high concentrations. © 2022, Academia Brasileira de Ciencias. All rights reserved.