The Effect of Ergothioneine on Clastogenic Potential and Mutagenic Activity

2011 ◽  
Vol 30 (4) ◽  
pp. 405-409 ◽  
Author(s):  
Alexander G. Schauss ◽  
Erzsébet Béres ◽  
Adél Vértesi ◽  
Zsuzsanna Frank ◽  
Ilona Pasics ◽  
...  
Keyword(s):  
Dietary Supplement ◽  
Micronucleus Test ◽  
Mutagenic Activity ◽  
Metabolic Activation ◽  
Chromosome Aberration Assay ◽  
Mammalian Erythrocyte ◽  
Polychromatic Erythrocytes ◽  
Structural Chromosome

L-(+)-ergothioneine has antioxidant and anti-inflammatory properties in vitro and in vivo and has uses as a dietary supplement and as an ingredient in foods, cosmetics, and as a pharmaceutical additive. The clastogenic potential and mutagenic of ergothioneine were assessed in vitro and in vivo. Ergothioneine concentrations up to 5000 μg/mL, with and without metabolic activation, was tested in the chromosome aberration assay with CHL cells and found not to induce structural chromosome aberrations. In the in vivo mammalian erythrocyte micronucleus test, ergothioneine was administered orally to male mice at doses up to 1500 mg/kg for potential genotoxic activity. No increase in the frequency of micronucleated polychromatic erythrocytes was observed.  Overall, ergothioneine was not genotoxic in these studies and provides additional experimental evidence supporting the safety of its use as a potential dietary supplement.

Genetic Toxicity Studies of the Ketogenic Ester Bis Hexanoyl (R)-1,3-Butanediol

2021 ◽  
pp. 109158182199177
Author(s):  
Brianna J. Stubbs ◽  
Andrey I. Nikiforov ◽  
Marisa O. Rihner ◽  
Sari Weston ◽  
Nancy Higley ◽  
...  
Keyword(s):  
Micronucleus Test ◽  
Mutagenic Activity ◽  
Metabolic Activation ◽  
Coli Strain ◽  
Control Group ◽  
Sprague Dawley ◽  
Genetic Toxicity ◽  
Polychromatic Erythrocytes

A series of studies was conducted to assess the genetic toxicity of a novel ketone ester, bis hexanoyl (R)-1,3-butanediol (herein referred to as BH-BD), according to Organization for Economic Co-operation and Development testing guidelines under the standards of Good Laboratory Practices. In bacterial reverse mutation tests, there was no evidence of mutagenic activity in any of the Salmonella typhimurium strains tested or in Escherichia coli strain WP2 uvrA, at dose levels up to 5,000 μg/plate in the presence or absence of Aroclor 1254-induced rat liver (S9 mix) for metabolic activation. In the in vitro micronucleus test using human TK6 cells, BH-BD did not show a statistically significant increase in the number of cells containing micronuclei when compared with concurrent control cultures at all time points and at any of the concentrations analyzed (up to 100 μg/mL, final concentration in culture medium), with and without S9 mix activation. In the in vivo micronucleus test using Sprague Dawley rats, BH-BD did not show a statistically significant increase in the incidence of micronucleated polychromatic erythrocytes relative to the vehicle control group. Therefore, BH-BD was concluded to be negative in all 3 tests. These results support the safety assessment of BH-BD for potential use in food.

scholarly journals In Vitro Genotoxicity Assessment from the Glycyrrhiza New Variety Extract

2021 ◽  
Vol 11 (21) ◽  
pp. 10257
Author(s):  
Young-Jae Song ◽  
Dong-Gu Kim ◽  
Jeonghoon Lee ◽  
Wonnam Kim ◽  
Hyo-Jin An ◽  
...  
Keyword(s):  
Ames Test ◽  
Micronucleus Test ◽  
Herbal Medicines ◽  
Mouse Bone Marrow ◽  
New Variety ◽  
Polychromatic Erythrocytes ◽  
Chromosome Aberration Test ◽  
In Vitro Genotoxicity

The various species that comprise the genus Glycyrrhiza (Licorice) have long been used as oriental herbal medicines in Asian countries. Wongam (WG), which is a new variety of Glycyrrhiza, was developed in Korea to overcome the limitations of low productivity, environmental restrictions, and an insufficient presence of glycyrrhizic acid and liquiritigenin. In this study, we evaluated WG extract’s genotoxicity through an in vitro bacterial reverse mutation (AMES) test, an in vitro chromosome aberration test, and an in vivo mouse bone marrow micronucleus test. In the AMES test, WG extract at concentrations of up to 5000 µg/plate showed no genotoxicity regardless of S9 mix. No chromosome aberrations appeared after 6 h in 1400 µg/mL WG extract regardless of S9 mix or in 1100 µg/mL WG extract after 24 h without S9 mix. Nor was there a significant increase in the number of micronucleated polychromatic erythrocytes to total erythrocytes up to 5000 mg/kg/day for 2 days detected in the micronucleus test. These results confirm that WG extract is safe for use as an herbal medicine, as it precipitates no detectable genotoxic effects.

Genotoxicity and Carcinogenicity Studies of Soy Isoflavones

2002 ◽  
Vol 21 (4) ◽  
pp. 277-285 ◽  
Author(s):  
R. R. Misra ◽  
S. D. Hursting ◽  
S. N. Perkins ◽  
N. Sathyamoorthy ◽  
J. C. Mirsalis ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Drug Product ◽  
Present Report ◽  
Phase 1 ◽  
Metabolic Activation ◽  
Soy Isoflavones ◽  
Oral Toxicity ◽  
Polychromatic Erythrocytes

The potential cancer preventive efficacy of soy isoflavones is being investigated in preclinical and phase 1 clinical studies sponsored by the U.S. National Cancer Institute. Although 90-day oral toxicity studies with PTI G-2535 (an investigational soy isoflavone drug product) in rats and dogs, as well as teratology studies, indicated no signs of toxicity, there remains a mechanistic concern associated with the ability of isoflavones (i.e., genistein) to inhibit topoisomerase, possibly leading to DNA strand breaks. The present report describes results from two in vitro genotoxicity studies, one in vivo genotoxicity study, and a single carcinogenicity study conducted in p53 knockout mice. Bacterial mutagenesis experiments using six tester strains without metabolic activation revealed no evidence that PTI G-2535 was mutagenic. In similar experiments with exogenous metabolic activation there were statistically significant increases in revertants, but less than twofold, in a single (Salmonella typhimurium TA100) tester strain. Mouse lymphoma cell mutagenesis experiments conducted with and without metabolic activation revealed statistically significant increases in mutation frequency at PTI G-2535 concentrations ≥ 0.8 and 12 μg/ml, respectively; such increases were dose related and increases in the frequency of both small and large colonies were observed. A statistically significant increase in the frequency of micronucleated polychromatic erythrocytes was also seen 24 hours after treatment in male, but not female, mice who received 500 and 1000 mg/kg body weight PTI G-2535; however, such increases were small, were not dose related, and were not observed 48 hours after treatment. In contrast, dietary genistein had no effect on survival, weight gain, or the incidence or types of tumors that developed in cancer-prone rodents lacking the p53 tumor suppressor gene, p53 knockout mice. The apparent risk/benefit of isoflavone ingestion may ultimately depend on the dose and developmental timing of exposure.

Mutagenic Activity of p-Toluenesulfonhydrazide

1992 ◽  
Vol 8 (6) ◽  
pp. 369-376 ◽  
Author(s):  
David H. Blakey ◽  
Earle R. Nestmann ◽  
Janet M. Bayley ◽  
K. Laurie Maus ◽  
George R. Douglas
Keyword(s):  
Chinese Hamster Ovary ◽  
Mutagenic Activity ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Gene Mutations ◽  
Metabolic Activation ◽  
High Volume ◽  
Ovary Cells

Toluenesulfonhydrazide (TSH) is a high volume production chemical for which there is relatively little toxicological data. In this study, the mutagenic activity of TSH was determined in the Salmonella/mammalian microsome assay and the in vitro chromosomal aberration assay using Chinese hamster ovary cells. TSH induced gene mutations both with and without metabolic activation in the Salmonella/mammalian microsome assay but that it did not induce chromosomal aberrations in Chinese hamster ovary cells. The results of this study indicate that TSH is an in vitro mutagen and should be assessed for in vivo mutagenicity.

scholarly journals Mutagenic activation of CL64,855, an anti-Trypanosoma cruzi nitroderivant, by bacterial nitroreductases

1998 ◽  
Vol 21 (4) ◽  
pp. 567-572 ◽  
Author(s):  
Marcos Antonio de Morais Jr. ◽  
Rita de Cássia Café Ferreira ◽  
Luiz Carlos de Souza Ferreira
Keyword(s):  
Trypanosoma Cruzi ◽  
Mutagenic Activity ◽  
Metabolic Activation ◽  
Extreme Resistance ◽  
Serum Samples ◽  
Killing Effect ◽  
Mutagenic Response ◽  
Induced Mutagenesis

CL64,855 is a nitroimidazole-thiodiazole derivate with high anti-Trypanosoma cruzi activity. CL64,855-induced mutagenesis in the Salmonella/microsome test was detected by TA98 and TA98dnp6 strains, but not by the nitroreductase I-deficient TA98nr strain. The lack of mutagenic response of TA98nr was connected with its extreme resistance to the killing effect of the drug. Presence of S9 mix did not restore mutagenic activity of CL64,855 to the TA98nr strain. Additionally, CL64,855 was reduced in vitro by the nitroreductase I-proficient TA98 strain, mainly in the presence of oxygen, but not by the TA98nr strain. Mutagenic activity was detected in serum samples of treated guinea pigs by nitroreductase-proficient strains TA98 and TA98dnp6, but not by nitroductase-deficient strain TA98nr. In the case of urine, mutagenic activity was observed with all three tested strains, suggesting an in vivo metabolic activation of the drug by a distinct metabolic pathway.

scholarly journals Assessment of genotoxicity and antigenotoxicity of an aqueous extract of Cleistocalyx nervosum var. paniala in in vitro and in vivo models

2012 ◽  
Vol 5 (4) ◽  
pp. 201-206 ◽  
Author(s):  
Suphachai Charoensin ◽  
Sirinya Taya ◽  
Sugunya Wongpornchai ◽  
Rawiwan Wongpoomchai
Keyword(s):  
Aqueous Extract ◽  
Micronucleus Test ◽  
Metabolic Activation ◽  
Toxicity Tests ◽  
Spectrometric Analysis ◽  
Ionization Mass ◽  
In Vivo Models ◽  
Micronucleus Formation

ABSTRACT Cleistocalyx nervosum var. paniala, an edible fruit found in Northern Thailand, contains high amounts of phenolic compounds with invitro antioxidant activity. The aqueous extract of the ripe fruit was evaluated for its safety and beneficial effects using genotoxicity and toxicity tests. The C. nervosum extract was not only non-mutagenic in Salmonella typhimurium strains TA98 and TA100 in the presence and absence of metabolic activation, but exhibited also moderate antimutagenic effects against aflatoxin B1 and 2-amino- 3,4-dimethylimidazo[4,5-f ]quinoline-induced mutagenesis. Electrospray ionization-mass spectrometric analysis revealed the major anthocyanins, which included cyanidin-3,5-diglucoside, cyanidin-3-glucoside and cyanidin-5-glucoside. The administration of C.nervosum at concentration of 5,000 mg/kg bw did not induce acute toxicity in rats. A liver micronucleus test was performed to detect clastogenicity and anticlastogenicity. The extract in the dose of 1,000 mg/kg did not cause micronucleus formation in the liver of rats. Furthermore, in rats administered 100-1,000 mg/kg of the extract, no anticlastogenic effect against diethylnitrosamine-induced hepatic micronucleus formation was observed. These studies provide data concerning the safety and antimutagenic potency of an aqueous extract of C. nervosum fruit.

scholarly journals Genotoxic properties of some organophosphate pesticides

2020 ◽  
pp. 72-73
Author(s):  
О.В. Егорова ◽  
Н.А. Илюшина ◽  
Н.С. Аверьянова ◽  
Л.А. Кара ◽  
Ю.В. Демидова ◽  
...  
Keyword(s):  
Ames Test ◽  
Micronucleus Test ◽  
Organophosphate Pesticides ◽  
Bacterial Strains ◽  
Technical Grade ◽  
Mammalian Erythrocyte ◽  
The Russian Federation ◽  
Mutagenic Effects

С использованием теста Эймса и микроядерного теста in vivo на эритроцитах млекопитающих изучена генотоксичность некоторых фосфорорганических пестицидов, применяемых в сельском хозяйстве. Технические продукты хлорпирифоса и диазинона не проявляли генотоксичности ни в условиях in vitro, ни in vivo. Выявлены слабые мутагенные эффекты диметоата на штаммах бактерий. Некоторые технические продукты глифосата, диметоата, а также пиримифос-метил индуцировали цитогенетические нарушения у мышей линии CD-1. Наблюдаемые эффекты in vivo были низкими даже на уровне максимальных переносимых доз, поэтому все исследованные фосфорорганические пестициды могут быть отнесены к 3 или 4 классам опасности по критерию «мутагенность» согласно принятой в Российской Федерации классификации. The genotoxicity of some organophosphate pesticides applied in agriculture was studied using the Ames test and the mammalian erythrocyte micronucleus test in vivo. Technical grade active ingredients (TGAI) of chlorpyrifos and diazinon did not show genotoxicity either in vitro or in vivo. The weak mutagenic effects of dimethoate were revealed with bacterial strains. Some TGAIs of glyphosate, dimethoate, and pyrimifos-methyl induced cytogenetic abnormalities in CD-1 mice. The observed effects in vivo were low even at the maximum tolerated doses. Therefore, according to the pesticide hygienic classification adopted in the Russian Federation all studied organophosphate pesticides can be assigned a 3 or 4 class of hazard upon the criterion “mutagenicity”.

scholarly journals Origanum majoranaEssential Oil Lacks Mutagenic Activity in theSalmonella/Microsome and Micronucleus Assays

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Andrea dos Santos Dantas ◽  
Luiz Carlos Klein-Júnior ◽  
Miriana S. Machado ◽  
Temenouga N. Guecheva ◽  
Luciana D. dos Santos ◽  
...  
Keyword(s):  
Essential Oil ◽  
Salmonella Typhimurium ◽  
Micronucleus Test ◽  
Mutagenic Activity ◽  
Chinese Hamster ◽  
Metabolic Activation ◽  
Lung Fibroblasts ◽  
Chromosome Mutation ◽  
Origanum Majorana

The present study aimed to investigate thein vitromutagenic activity ofOriganum majoranaessential oil. The most abundant compounds identified by GC-MS wereγ-terpinene (25.73%),α-terpinene (17.35%), terpinen-4-ol (17.24%), and sabinene (10.8%). Mutagenicity was evaluated by theSalmonella/microsome test using the preincubation procedure on TA98, TA97a, TA100, TA102, and TA1535Salmonella typhimuriumstrains, in the absence or in the presence of metabolic activation. Cytotoxicity was detected at concentrations higher than 0.04 μL/plate in the absence of S9 mix and higher than 0.08 μL/plate in the presence of S9 mix and no gene mutation increase was observed. For thein vitromammalian cell micronucleus test, V79 Chinese hamster lung fibroblasts were used. Cytotoxicity was only observed at concentrations higher than or equal to 0.05 μg/mL. Moreover, when tested in noncytotoxic concentrations,O. majoranaessential oil was not able to induce chromosome mutation. The results from this study therefore suggest thatO. majoranaessential oil is not mutagenic at the concentrations tested in theSalmonella/microsome and micronucleus assays.

Toxicology of Diethylene Glycol Butyl Ether 3. Genotoxicity Evaluation in an In Vitro Gene Mutation Assay and an In Vivo Cytogenetic Test

1993 ◽  
Vol 12 (2) ◽  
pp. 155-159 ◽  
Author(s):  
B. Bhaskar Gollapudi ◽  
V. A. Linscombe ◽  
M. L. Mcclintock ◽  
A. K. Sinha ◽  
C. R. Stack
Keyword(s):  
Bone Marrow ◽  
Gene Mutation ◽  
Micronucleus Test ◽  
Mouse Bone Marrow ◽  
Butyl Ether ◽  
Polychromatic Erythrocytes ◽  
Mutation Assay ◽  
Gene Mutation Assay

DGBE was evaluated in a forward gene mutation assay at the HGPRT locus of CHO cells in culture and in an in vivo mouse bone marrow micronucleus test for cytogenetic damage. DGBE did not elicit a positive response in the CHO/HGPRT assay when tested up to a maximum concentration of 5000 μg/ml with and without an external metabolic activation system (S-9). In the micronucleus test employing three post-treatment bone marrow sampling times (24, 48, and 72 hr), DGBE was ineffective in increasing the incidence of micronucleated polychromatic erythrocytes (MN-PCE) when tested in both sexes up to a maximum tolerated dose of 3300 mg/kg body weight. Thus, these data and those of others indicate a general lack of genotoxic potential for DGBE in short-term tests.

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