TA-100 FGFR3 decoy / Pfizer - LARVOL DELTA

Is a liver comparable to a liver? A comparison of different rat-derived S9-fractions with a biotechnological animal-free alternative in the Ames fluctuation assay. (PubMed, Sci Total Environ) - "To gain more insight into these variances, three different but commonly used rat-derived S9-fractions were compared in the present study for their variance and performance with a reference compound in the Ames fluctuation assay with Salmonella typhimurium strains TA 98 and TA 100 according to ISO 11350...EwoS9R was evaluated as a promising approach in the Ames fluctuation assay with 5 compounds observed to have similar results with both rat-derived S9-fraction and ewoS9R (41%), for 3 compounds ewoS9R was a better metabolization system than the rat-derived S9-fraction (16%). Further research is necessary to determine the full potential of ewoS9R in comparison to rat-derived S9-fractions."

Journal

Structures-activity relationship (SAR) studies on the mutagenic properties of 2,7-diaminofluorene and 2,7-diaminocarbazole derivatives. (PubMed, Bioorg Med Chem Lett) - "To avoid the mutagenesis issue of these core structures, we examined various functional groups at the C9 or N9 position of 2,7-diaminofluorene or 2,7-diaminocarbazole, respectively, through the Ames test in TA98 and TA100 mutants of Salmonella typhimurium LT-2. We discovered that, through proper alkyl substitution at the C9 or N9 position, 2,7-diaminofluorene and 2,7-diaminocarbazole moieties can be successfully employed in drug discovery without necessarily causing mutagenicity problems."

Journal

Evaluation of effect of hazardous contaminants in areas for the abstraction of drinking water. (PubMed, Environ Res) - "Mutagenic effects were evaluated by Salmonella/microsome assay using TA98, TA97a, TA100, YG1041 and YG1042 strains in the presence and absence of metabolic activation (S9)...The test performed on Danio rerio embryos (FET) in the in natura water samples did not present significant responses. Chemical analyses of polycyclic aromatic hydrocarbons and metals already identified as chemical markers in the area indicated a small contribution to the mutagenic potency, calling attention to the fact that other direct-acting pollutants may be present at the drinking water abstraction sites."

Journal

The first report to evaluate safety of cyanobacterium Leptolyngbya sp. KIOST-1 for use as a food ingredient: Oral acute toxicity and genotoxicity study. (PubMed, J Microbiol Biotechnol) - "Genotoxicity was assessed using a bacterial reverse mutation test with Salmonella typhimurium (strains TA98, TA100, TA1535, and TA1537) and Escherichia coli WP2 uvrA, an in vitro mammalian chromosome aberration test using Chinese hamster lung cells, and an in vivo mammalian erythrocyte micronucleus test using Hsd:ICR (CD-1) SPF mouse bone marrow...The chromosome aberration test and micronucleus assay demonstrated no chromosomal abnormalities and genotoxicity, respectively, in the presence of the LK1 powder. The absence of physiological findings and genetic abnormalities suggests that LK1 powder is appropriate as a candidate biomass to be used as a safe food ingredient."

Clinical • Journal

Evaluation of the Acute Toxicity and Genotoxicity of the Rice Biofortified with β-Glucan (PubMed, Sichuan Da Xue Xue Bao Yi Xue Ban) - "Whether with S activation or not, no genotoxicity was found to the tested strains TA97a, TA98, TA100, TA102 and TA1535. All results of the three genotoxicity tests were negative. Under the current experimental conditions, β-glucan biofortified rice showed no obvious acute toxicity and genotoxicity."

Journal • Hematological Malignancies • Lymphoma • Oncology

Genotoxic activities of wastewater after ozonation and activated carbon filtration: Different effects in liver-derived cells and bacterial indicators. (PubMed, Water Res) - "We found no evidence for mutagenic effects of non-ozonated samples in several bacterial tester strains (TA98, TA100, YG7108, YG7104, YG7112 and YG7113) but clear induction of His mutants after O treatment in two strains with defective genes encoding for DNA repair, which are highly sensitive towards alkylating agents (YG7108 and YG7104)...None of the waters caused acute toxicity in the liver-derived cells and in the bacterial indicators. Assuming that hepatic mammalian cells reflect the genotoxic properties of the waters in vertebrates (including humans) more adequately as genetically modified bacterial indicators, we conclude that ozonation has beneficial effects in regard to the reduction of genotoxic properties of treated wastewaters."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Solid Tumor

Mutagenicity and genotoxicity assessment of a new biopreservative product rich in Enterocin AS-48. (PubMed, Food Chem Toxicol) - "To assess its potential as food additive, the mutagenicicity and genotoxicity has been assayed by means of the bacterial reverse-mutation assay in Salmonella typhimurium TA97A, TA98, TA100, TA102, TA1535 strains (Ames test, OECD 471) and the micronucleus test (MN) (OECD 487) in L5178Y/ Tk+/- cells. Negative results in the mutagenicity and genotoxicity assays point out the good safety profile of the byproduct and support its use as additive. Further toxicological studies are required before its approval and commercial application."

Journal

Gamma and UV radiations induced treatment of anti-cancer methotrexate drug in aqueous medium: Effect of process variables on radiation efficiency evaluated using bioassays. (PubMed, Appl Radiat Isot) - "This studystudy focuses on the effect of radiation treatment and hydrogen peroxide (HO) on the toxicity of anticancer methotrexate. The mutagenicity reduced up to 82.3, 86.46 and 89.59% (TA98) and 85.42, 87.5 and 90.63% (TA100) for UV/HO while 89.59, 90.63 and 93.75% (TA98) and 84.38, 89.59 and 92.71% (TA100) for gamma/HO. The UV and gamma radiation along with HO based AOPs are promising approaches to detoxify the wastewater which can be extended to real hospital liquid effluent effectively."

Journal • Hematological Disorders • Oncology

Genotoxicity and glucose tolerance induction by acetyltriethylcitrate, substitute plasticizer compared to di(2-ethylhexyl)phthalate. (PubMed, Sci Rep) - "Genotoxicity was determined by Ames test with histidine-requiring Salmonella typhimurium (TA98, TA100, TA1535 and TA1537) and tryptophan-requiring Escherichia coli (WP2uvrA(pKM101)) strains, chromosomal aberration assay with Chinese hamster lung(CHL/IU) cells, and micronucleus test with bone marrow cells of CD-1 mice...Then, taken together, our results suggest that ATEC could disrupt glucose metabolism under our experimental conditions. Therefore, although DEHP and ATEC may not be genotoxic, our data should be helpful for persons with the problem in glucose metabolism to choose products containing DEHP or ATEC."

Journal

Influence of the UV-Vis irradiation on the acute toxicity to zebrafish and mutagenicity of the selected psychotropic drugs. (PubMed, J Environ Sci Health A Tox Hazard Subst Environ En) - "The influence of the UV-Vis radiation on the toxicity of agomelatine, loxapine, clozapine and tiapride was studied...The phototransformation of clozapine did not alter the mutagenicity and decreased the acute toxicity to the zebrafish larvae. In silico calculations showed a satisfactory prediction ability in some instances, especially in the case of mutagenic potential of the tiapride phototransformation products."

Journal

Nonclinical evaluation of IQG-607, an anti-tuberculosis candidate with potential use in combination drug therapy. (PubMed, Regul Toxicol Pharmacol) - "Importantly, IQG-607 had additive effects when combined with the first-line anti-tuberculosis drugs rifampin and pyrazinamide in mice...The Salmonella mutagenicity test revealed that IQG-607 induced base pair substitution mutations in the strains TA100 and TA1535...Additionally, IQG-607 did not increase micronucleus frequencies in mice, at any dose tested, 25, 100, or 250 mg/kg. The favorable activity in combination with first-line drugs and mild to moderate toxic events described in this study suggest that IQG-607 represents a candidate for clinical development."

Journal • Infectious Disease • Tuberculosis

Toxicity assessment of Gryllus bimaculatus (a type of cricket) glycosaminoglycan. (PubMed, Toxicol Res) - "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)...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."

Journal • Hematological Disorders • Ophthalmology

Modulation of mutagenicity in Salmonella typhimurium and antioxidant properties and antiproliferative effects of fractions from Cassia fistula L. on human cervical HeLa and breast MCF-7 cancer cells. (PubMed, Environ Sci Pollut Res Int) - "S9-independent, namely 4-nitro-o-phenylenediamine (TA98) and sodium azide (TA100) and S9-dependent, 2-AF (2-aminofluorene)...The HPLC analysis of CaLE revealed the presence of catechin, epiafzelechin, and chlorogenic acid which are responsible for its antimutagenic and antiproliferative efficacy. Graphical abstract."

Journal • Breast Cancer • Oncology

Phytochemical composition and in vitro safety evaluation of Ziziphora clinopodioides Lam. ethanolic extract: cytotoxicity, genotoxicity and mutagenicity assessment. (PubMed, J Ethnopharmacol) - "Results indicated a dose-dependent cytotoxicity and genotoxicity potential of the EEZC on human lymphocytes, suggesting that this plant should be used with caution by consumers, even in the food and pharmaceutical industries. Since the plant usage in daily life continues to increase due to its ever growing phytotherapical and phytonutritional properties, it may pose a health risk by its high concentration's uptake. Although no mutagenicity of this extract was observed in this study, further research is recommended to clarify the mutagenic risks of this herb."

Journal

Antioxidant Phytoconstituents From Onosma bracteata Wall. (Boraginaceae) Ameliorate the CCl Induced Hepatic Damage: In Vivo Study in Male Wistar Rats. (PubMed, Front Pharmacol) - "The Obeth modulated mutagenicity of 2 Aminofluorine (2AF) in the pre-incubation mode of investigation (EC 10.48 µg/0.1 mL/plate) in TA100 strain of Salmonella typhimurium...HPLC data analysis showed the supremacy of major compounds namely, catechin, kaempferol, epicatechin, and Onosmin A in Obeth. The present investigation establishes the hepatoprotective and chemopreventive potential of O. bracteata against CCl-induced hepatotoxicity via antioxidant defense system and modulation of the expression of proteins associated with the process of carcinogenesis in hepatic cells."

Journal • Preclinical • Asthma • Hepatology • Inflammation • Oncology • Respiratory Diseases • Rheumatology • NFKB1 • TP53

Thermal Processing for the Release of Phenolic Compounds from Wheat and Oat Bran. (PubMed, Biomolecules) - "Both thermally processed matrices had strong antimutagenic activity toward S. typhimurium TA100. This thermal processing was tested on bran based on its practical application within the food industry, considering the design of different cereal byproducts derived from functional foods and nutraceuticals."

Journal

The Chemical and Biological Profiles of Leaves from Commercial Blueberry Varieties. (PubMed, Plants (Basel)) - "The blueberry leaf extracts had a strong antibacterial activity and a low antifungal capacity, and a low-to-moderate antimutagenic capacity towards Salmonella typhimurium TA98 and TA100 strains, with Toro leaf being the best candidate. All of these biological activities indicate health-related benefits, recommending them as suitable candidates for medical and pharmaceutical applications. The present paper adds significant knowledge to the field of blueberry leaves via chemical and biological profiles, supporting the ultrasound-assisted extraction technique as a useful and green method to provide alternative sources of bioactive compounds."

Journal

Chemical Characterization, Antioxidant, Enzyme Inhibition and Antimutagenic Properties of Eight Mushroom Species: A Comparative Study. (PubMed, J Fungi (Basel)) - "acutoconica, in particular depicted excellent antimutagenicity with a ratio of 97% for TA100 and with a rate of 96% for TA98 strain against mutagens in the presence of metabolic activation system. Results presented in this study tend to show that the mushroom species could be exploited as potential sources of therapeutic bioactive agents, geared towards the management of oxidative stress, global health problems and cancer."

Journal • Oncology • Pain • Tyrosinase

Toxicity, mutagenicity and stability assessment of simply produced electrolyzed water as a wound healing agent in vitro. (PubMed, Hum Exp Toxicol) - "Likewise, with/ without metabolic activation, neither of EWs had shown mutagenic profile in TA 98 and TA100 strains of Salmonella typhimurium. Follow-up of ORP (oxidation-reduction potential), pH and FCC (free chlorine concentration) showed that temperature and light were important storage conditions to maintain a stable profile particularly for ORP and FCC, which are the most important indicators for biological activity of EW. According to the present findings, it can be suggested that particularly StAEW, may represent a valuable wound healing agent with an achievable, economical and easy production system when stored under proper conditions."

Journal • Preclinical

Evaluation of 2-methoxy-4-nitroaniline (MNA) in hypersensitivity, 14-day subacute, reproductive, and genotoxicity studies. (PubMed, Toxicology) - "In bacterial mutagenicity assays, MNA (250-1000 μg/plate) induced significant increases compared to control in mutant colonies with and without metabolic activation enzymes in Salmonella typhimurium strains TA100 and TA98. These data indicate that MNA is genotoxic, and may induce erythrocyte damage and reactive phagocytosis by macrophages in the liver and spleen."

Journal • Immunology • Myocardial Infarction

Optimization of a pre-metabolization procedure using rat liver S9 and cell-extracted S9 in the Ames fluctuation test. (PubMed, Sci Total Environ) - "After pre-incubation with S9 fraction, chemicals induced bacteria revertants in both the TA98 and the TA100 assay as efficiently as the standard Ames assay. The pre-incubation of chemicals with S9 fraction could serve for a wide range of cellular in vitro assays to efficiently combine activation and toxicity measurement, which may greatly facilitate the application of these assays for chemical hazard assessment and monitoring of environmental samples."

Journal • Preclinical

Genome-wide somatic mutation analysis via Hawk-Seq™ reveals mutation profiles associated with chemical mutagens. (PubMed, Arch Toxicol) - "Genomic mutations in gpt delta mice or Salmonella typhimurium TA100 exposed to methylnitrosourea (MNU), ethylnitrosourea (ENU), diethylnitrosamine (DEN), benzo[a]pyrene (BP), and aristolochic acid (AA) were profiled using Hawk-Seq™ to analyse positions, substitution patterns, or frequencies...Meanwhile, signatures attributable to ENU and DEN were highly similar to each other, but not to signature 11, suggesting that the mechanisms of these agents differed from those of typical alkylating agents. Thus, Hawk-Seq™ can clarify genome-wide chemical mutagenicity profiles at extraordinary resolutions, thereby providing insight into mutagen mechanisms and their roles in cancer development."

Biomarker • Journal • Oncology

Cytochrome P450 inhibition potential and initial genotoxic evaluation of 14-O-[(4,6-diaminopyrimidine-2-yl)thioacetyl] mutilin. (PubMed, Sci Rep) - "In the Ames test, Salmonella strains TA97, TA98, TA100, TA102 and TA1535 were treated with or without the metabolic activation (S9). Analysis showed the average number of revertant colonies per plate was less in double in the groups treated with DPTM than that in the negative control plate and showed no dose-related increase."

Journal • CYP1A2 • CYP2E1 • CYP3A4

[VIRTUAL] Preclinical Profile of a Novel Immunomodulatory Compound AVR-48 to Prevent Bronchopulmonary Dysplasia (ATS-I 2020) - "Methodology: To determine the genetic toxicity of AVR-48, Ames bacterial mutation (TA 98 and TA 100, 700 μg/well) and invitro micronucleus (IMN, 1.0 mM) assays were conducted... AVR-48 is a promising therapeutic against BPD and exhibits an acceptable safety profile with good PK/PD correlation in rodent plasma and BALF. Further toxicokinetic and efficacy studies are in progress in dog and pre-term lamb models respectively."

IO Biomarker • Preclinical • Asthma • Bronchopulmonary Dysplasia • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immune Modulation • Immunology • Inflammation • Respiratory Diseases • TLR4

Comparative Toxigenicity and Associated Mutagenicity of Aspergillus fumigatus and Aspergillus flavus Group Isolates Collected from the Agricultural Environment. (PubMed, Toxins (Basel)) - "The Ames test was performed on Salmonella typhimurium strains TA98, TA100 and TA102, without and with S9mix (exogenous metabolic activation system). On the other hand, AFB and AFM modulate negatively the mutagenicity of AFB when mixed in binary or tertiary mixtures. Thus, the evaluation of the mutagenicity of "natural" mixtures is an integrated parameter that better reflects the potential impact of exposure to toxigenic Aspergilli."

Journal