Evidence for an Aneugenic Mechanism of Action for Micronucleus Induction by Black Cohosh Extract.

Abstract:

:Black cohosh extract (BCE) is a popular botanical dietary supplement marketed to relieve symptoms of various gynecological ailments. Studies conducted by the National Toxicology Program (NTP) showed that BCE induces micronucleated erythrocytes in female rats and mice. Subsequently, the NTP showed that a variety of BCEs, including the sample that induced micronuclei (MN) in vivo ("NTP BCE") had a similar effect in human TK6 cells. Further testing with the MultiFlow® DNA Damage Assay revealed that TK6 cells exposed to NTP BCE, as well as a BCE reference material (BC XRM), exhibited a signature consistent with aneugenic activity in TK6 cells. Results from experiments reported herein confirmed these in vitro observations with NTP BCE and BC XRM. We extended these studies to include a novel test system, the MultiFlow Aneugen Molecular Mechanism Assay. For these experiments, TK6 cells were exposed to NTP BCE and BC XRM over a range of concentrations in the presence of fluorescent Taxol (488 Taxol). After 4 h, nuclei from lysed cells were stained with a nucleic acid dye and labeled with fluorescent antibodies against phospho-histone H3 (p-H3) and Ki-67. Whereas BCEs did not affect p-H3:Ki-67 ratios (a signature of aneugenic mitotic kinase inhibitors), 488 Taxol-associated fluorescence (a tubulin binder-sensitive endpoint) was affected. More specifically, 488 Taxol-associated fluorescence was reduced over the same concentration range that was previously observed to induce MN. These results provide direct evidence that BCEs destabilize microtubules in vitro, and this is the molecular mechanism responsible for the aneugenicity findings. Environ. Mol. Mutagen. 2019. © 2019 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

journal_name

Environ Mol Mutagen

authors

Bernacki DT,Bryce SM,Bemis JC,Dertinger SD,Witt KL,Smith-Roe SL

doi

10.1002/em.22334

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

845-856

issue

9

eissn

0893-6692

issn

1098-2280

journal_volume

60

pub_type

杂志文章
  • Generation of loss of heterozygosity and its dependency on p53 status in human lymphoblastoid cells.

    abstract::Loss of heterozygosity (LOH) is a critical event in the development of human cancers. LOH is thought to result from either a large deletion or recombination between homologous alleles during repair of DNA double-strand breaks (DSBs). These types of genetic alterations produce mutations in the TK gene mutation assay, w...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章,评审

    doi:10.1002/em.20113

    authors: Honma M

    更新日期:2005-03-01 00:00:00

  • The in vivo Pig-a gene mutation assay is useful for evaluating the genotoxicity of ionizing radiation in mice.

    abstract::The in vivo Pig-a mutation assay has been adapted for measuring mutation in rats, mice, monkeys, and humans. To date, the assay has been used mainly to assess the mutagenicity of chemicals that are known to be powerful point mutagens. The assay has not been used to measure the biological effects associated with ionizi...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.21724

    authors: Ohtani S,Unno A,Ushiyama A,Kimoto T,Miura D,Kunugita N

    更新日期:2012-10-01 00:00:00

  • Sources of polycyclic aromatic hydrocarbon exposure in non-occupationally exposed Koreans.

    abstract::Urinary 1-hydroxypyrene (1-OHP), an exposure biomarker for polycyclic aromatic hydrocarbons (PAHs), was used to identify potential sources of PAH exposure for 660 Koreans who were not occupationally exposed to PAHs (65% male; 35% female; mean age, 36.5 +/- 11.1 years). In this study, 74% of subjects had detectable lev...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.10196

    authors: Yang M,Kim S,Lee E,Cheong HK,Chang SS,Kang D,Choi Y,Lee SM,Jang JY

    更新日期:2003-01-01 00:00:00

  • Global gene expression response of a population exposed to benzene: a pilot study exploring the use of RNA-sequencing technology.

    abstract::The mechanism of toxicity of the leukemogen benzene is not entirely known. This pilot study used RNA-sequencing (RNA-seq) technology to examine the effect of benzene exposure on gene expression in peripheral blood mononuclear cells obtained from 10 workers occupationally exposed to high levels of benzene (≥5 ppm) in a...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.21801

    authors: Thomas R,McHale CM,Lan Q,Hubbard AE,Zhang L,Vermeulen R,Li G,Rappaport SM,Yin S,Rothman N,Smith MT

    更新日期:2013-08-01 00:00:00

  • Mutagenicity of N- and O-acetyl derivatives of methyl 3,4-diphenyl-5-hydroxylamino-2-furoate and N-hydroxy-4-aminobiphenyl in Salmonella typhimurium.

    abstract::Methyl 3,4-diphenyl-5-hydroxylamino-2-furoate (N-OH-MDPF) (I), methyl 3,4-diphenyl-5-acetoxyamino-2-furoate (N-OAc-MDPF) (II), methyl 3,4-diphenyl-N-hydroxy-5-acetylamino-2-furoate (N-OH-MDPAF) (III), and methyl 3,4-diphenyl-N-acetoxy-5-acetylamino-2-furoate (N-OAc-MDPAF) (IV) were synthesized and tested for mutagenic...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.2850170204

    authors: Swaminathan S,Hatcher JF,Yamamoto K,Tanaka A,Ichikawa M,Bryan GT

    更新日期:1991-01-01 00:00:00

  • Reactive species and mitochondrial dysfunction: mechanistic significance of 4-hydroxynonenal.

    abstract::Mitochondrial dysfunction is a global term used in the context of "unhealthy" mitochondria. In practical terms, mitochondria are extremely complex and highly adaptive in structure, chemical and enzymatic composition, subcellular distribution and functional interaction with other components of cells. Consequently, alte...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章,评审

    doi:10.1002/em.20553

    authors: Roede JR,Jones DP

    更新日期:2010-06-01 00:00:00

  • Micronucleus induction by metronidazole in rat vaginal mucosa.

    abstract::Metronidazole (MTZ) is used for the treatment of many infectious diseases, including vaginal infections. While data indicate that MTZ is mutagenic and induces micronuclei in rodents, there is no information on the genotoxicity of MTZ in epithelial vaginal cells or cervical cells. In the present study, we have instille...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.20214

    authors: Ornelas-Aguirre JM,Gómez-Meda BC,Zamora-Perez AL,Ramos-Ibarra ML,Batista-González CM,Zúñiga-González GM

    更新日期:2006-06-01 00:00:00

  • Mechanism of induction of chromosomal aberrations by inhibitors of DNA topoisomerases.

    abstract::Evidence is provided that antitopoisomerase drugs induce chromosomal aberrations via the formation of DNA double strand breaks. Camptothecin, an inhibitor of DNA topoisomerase I, produced only chromatid-type aberrations, and in order to be effective it has to be present during the DNA replication. The fact that it ind...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章,评审

    doi:10.1002/em.2850220416

    authors: Palitti F

    更新日期:1993-01-01 00:00:00

  • Genetic and environmental influences on baseline SCE.

    abstract::Previous population-based studies have identified subject characteristics that, when combined, can account for approximately 20% of the observed interindividual variation in baseline SCE rates. In the present investigation, a classic twin study design was used to address the issue of the relevance of genetic factors t...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.2850200103

    authors: Hirsch BA,Sentz KK,McGue M

    更新日期:1992-01-01 00:00:00

  • DNA adducts of 1,3-butadiene in humans: relationships to exposure, GST genotypes, single-strand breaks, and cytogenetic end points.

    abstract::The modulation of 1,3-butadiene (BD)-induced DNA adducts by occupational exposure, glutathione S-transferase (GST) genotypes, single-strand breaks, and cytogenetic end points was studied in 15 workers and 11 controls. The exposed group consisted of 8 smokers and 7 nonsmokers, whereas the control group consisted of 7 n...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.1031

    authors: Zhao C,Vodicka P,Sram RJ,Hemminki K

    更新日期:2001-01-01 00:00:00

  • Cytogenetic biomonitoring in traffic police workers: micronucleus test in peripheral blood lymphocytes.

    abstract::Atmospheric pollution represents a relevant environmental hazard which has been associated with considerable excess mortality, morbidity, and increased rates of respiratory diseases in humans. To date, more than 3,000 environmental chemical compounds have been identified in the ambient atmosphere, including a variety ...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:

    authors: Bolognesi C,Merlo F,Rabboni R,Valerio F,Abbondandolo A

    更新日期:1997-01-01 00:00:00

  • Structure-activity relationship of genotoxic polycyclic aromatic nitro compounds: further evidence for the importance of hydrophobicity and molecular orbital energies in genetic toxicity.

    abstract::A quantitative structure-activity relationship (QSAR) has been formulated for 15 polycyclic aromatic nitro compounds acting on E. coli PQ37. Upon damage of DNA by these substances beta-galactosidase is induced and can be easily assayed colorimetrically, hence, this is a short-term test for mutagenicity. The QSAR (log ...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.2850200210

    authors: Debnath AK,Hansch C

    更新日期:1992-01-01 00:00:00

  • Novel DNA repair alkyltransferase from Caenorhabditis elegans.

    abstract::O6-alkylguanine DNA-alkyltransferase (AGT) is a widely distributed DNA repair protein that protects living organisms from endogenous and exogenous alkylation damage to DNA at the O6-position of guanine. The search of the C. elegans genome database for an AGT protein revealed the presence of a protein (cAGT-2) with som...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.1077

    authors: Kanugula S,Pegg AE

    更新日期:2001-01-01 00:00:00

  • Glycosylphosphatidylinositol (GPI) anchored protein deficiency serves as a reliable reporter of Pig-a gene Mutation: Support from an in vitro assay based on L5178Y/Tk+/- cells and the CD90.2 antigen.

    abstract::Lack of cell surface glycosylphosphatidylinositol (GPI)-anchored protein(s) has been used as a reporter of Pig-a gene mutation in several model systems. As an extension of this work, our laboratory initiated development of an in vitro mutation assay based on the flow cytometric assessment of CD90.2 expression on the c...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.22154

    authors: Bemis JC,Avlasevich SL,Labash C,McKinzie P,Revollo J,Dobrovolsky VN,Dertinger SD

    更新日期:2018-01-01 00:00:00

  • Genetic toxicology testing of the antimalarial drugs chloroquine and a new analog, AQ-13.

    abstract::AQ-13 ([N1-(7-chloro-quinolin-4yl)-3-(N3,N3-diethylamino)propylamine] dihydrochloride trihydrate) is an aminoquinoline antimalarial drug that is effective against chloroquine-resistant strains of Plasmodium falciparum. It is structurally similar to the widely used chloroquine diphosphate (CQ). We evaluated these drugs...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.1052

    authors: Riccio ES,Lee PS,Winegar RA,Krogstad DJ,De D,Mirsalis JC

    更新日期:2001-01-01 00:00:00

  • Comparison of mutagenicity and calf thymus DNA adducts formed by the particulate and semivolatile fractions of vehicle exhausts.

    abstract::In this study we compared the ability of extractable organic material from particulate and semivolatile fractions of gasoline emission to induce mutations in bacteria and form adducts with calf thymus (CT) DNA with corresponding data obtained from diesel exhaust. Exhaust particles from gasoline-powered passenger cars ...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.10172

    authors: Pohjola SK,Lappi M,Honkanen M,Savela K

    更新日期:2003-01-01 00:00:00

  • Analysis of bleomycin-induced mutagenic functions related to the PSO4 (= xs9) gene of Saccharomyces cerevisiae.

    abstract::In the present work we analyse some properties of the pso4-1 (= xs9) mutant of the yeast Saccharomyces cerevisiae, which is blocked in both reverse mutation and recombination. We have applied the "apparent survival test" as a method to characterize putative inducible error-prone repair activities related to the PSO4 g...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.2850180204

    authors: Severgnini A,Lillo O,Nunes E

    更新日期:1991-01-01 00:00:00

  • DNA damage in peripheral blood leukocytes of physically active individuals as measured by the alkaline single cell gel electrophoresis assay.

    abstract::DNA damage induced by physical activity and/or exercise has been reported under different conditions but not for individuals maintaining physical fitness by regular strenuous exercise. Therefore, we compared levels of DNA damage in blood leukocytes of 40 healthy individuals (35 males, 5 females) who regularly exercise...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.20457

    authors: Gandhi G,Chopra G

    更新日期:2009-05-01 00:00:00

  • Pig-a gene mutation and micronucleated reticulocyte induction in rats exposed to tumorigenic doses of the leukemogenic agents chlorambucil, thiotepa, melphalan, and 1,3-propane sultone.

    abstract::To evaluate whether blood-based genotoxicity endpoints can provide temporal and dose-response data within the low-dose carcinogenic range that could contribute to carcinogenic mode of action (MoA) assessments, we evaluated the sensitivity of flow cytometry-based micronucleus and Pig-a gene mutation assays at and below...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.21846

    authors: Dertinger SD,Phonethepswath S,Avlasevich SL,Torous DK,Mereness J,Cottom J,Bemis JC,Macgregor JT

    更新日期:2014-05-01 00:00:00

  • Intralitter variation in murine fetal sister chromatid exchange responses to the transplacental carcinogen ethyl carbamate.

    abstract::Gravid Swiss Webster dams were injected via tail vein with a single (1.1, 2.2, or 3.3 mmol/kg) dose of ethyl carbamate (urethane) on days 13-17 of pregnancy. Relative sister chromatid exchange (SCE) responses in maternal bone marrow vs. individual fetal liver cells were assessed. In addition, in order to evaluate the ...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.2850140204

    authors: Neeper-Bradley TL,Conner MK

    更新日期:1989-01-01 00:00:00

  • The SOS system: A complex and tightly regulated response to DNA damage.

    abstract::Genomes of all living organisms are constantly threatened by endogenous and exogenous agents that challenge the chemical integrity of DNA. Most bacteria have evolved a coordinated response to DNA damage. In Escherichia coli, this inducible system is termed the SOS response. The SOS global regulatory network consists o...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章,评审

    doi:10.1002/em.22267

    authors: Maslowska KH,Makiela-Dzbenska K,Fijalkowska IJ

    更新日期:2019-05-01 00:00:00

  • Specific numerical chromosomal aberrations induced by adriamycin.

    abstract::Fluorescence in situ hybridization with 7, 17, X, and Y chromosome-specific DNA probe was used to investigate the ability of Adriamycin (AM) to induce aneuploidy in interphase human lymphocytes. The reliability of the probes was tested by hybridization to metaphases and interphase nuclei of untreated normal lymphocyte...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-2280(1999)33:2<161::aid-em8>3.0

    authors: Aly MS,Othman OE,El Nahas SM

    更新日期:1999-01-01 00:00:00

  • Bacterial and mammalian-cell genotoxicity of mixtures of chlorohydroxyfuranones, by-products of water chlorination.

    abstract::The genotoxic responses of mixtures of four chlorohydroxyfuranones (CHFs), 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), 3,4-dichloro-5-hydroxy-2(5H)-furanone (MCA), 3-chloro- 4-(chloromethyl)-5-hydroxy-2(5H)-furanone (CMCF) and 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone (MCF), were compared with the geno...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.20017

    authors: Mäki-Paakkanen J,Komulainen H,Kronberg L

    更新日期:2004-01-01 00:00:00

  • APRT: a versatile in vivo resident reporter of local mutation and loss of heterozygosity.

    abstract::We describe an in vivo mutagenesis model that utilizes reverse mutation and forward mutation at the endogenous Aprt locus. Reverse mutation provides an in situ method for detecting environments or agents that cause point mutations. Forward mutation detects large chromosomal events, including mitotic recombination, chr...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2280(1996)28:4<471::AID-EM25>3.

    authors: Stambrook PJ,Shao C,Stockelman M,Boivin G,Engle SJ,Tischfield JA

    更新日期:1996-01-01 00:00:00

  • Prevention of exposure to mutagenic fumes produced by hot cooking oil in Taiwanese kitchens.

    abstract::We evaluated the mutagens in fumes produced by heating three different cooking oils used in Taiwan to temperatures of 100 degrees C, 200 degrees C, and 300 degrees C, and constructed models to study the efficacy of fume extractors used commonly by Taiwanese women. Particulates of volatile emissions from lard (at 200 d...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:

    authors: Chiang TA,Wu PF,Ko YC

    更新日期:1998-01-01 00:00:00

  • Mitochondrial DNA: Epigenetics and environment.

    abstract::Maintenance of the mitochondrial genome is essential for proper cellular function. For this purpose, mitochondrial DNA (mtDNA) needs to be faithfully replicated, transcribed, translated, and repaired in the face of constant onslaught from endogenous and environmental agents. Although only 13 polypeptides are encoded w...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章,评审

    doi:10.1002/em.22319

    authors: Sharma N,Pasala MS,Prakash A

    更新日期:2019-10-01 00:00:00

  • Telomere measurement in individuals occupationally exposed to pesticide mixtures in tobacco fields.

    abstract::Occupational exposure to pesticides in tobacco fields causes genetic damage in farmers. The aim of this study was to analyze tobacco farmers chronically exposed to low doses of pesticides and nicotine (present in the tobacco leaves) in relation to absolute telomere length (aTL), and explore the influence of lifestyle ...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.21984

    authors: Kahl VF,Simon D,Salvador M,Branco Cdos S,Dias JF,da Silva FR,de Souza CT,da Silva J

    更新日期:2016-01-01 00:00:00

  • Novel transgenic rat for in vivo genotoxicity assays using 6-thioguanine and Spi- selection.

    abstract::Transgenic rodents are valuable models for investigating the genotoxicity of chemicals in vivo. Here, we report the establishment of a novel transgenic rat for genotoxicity analysis. In this model, about 10 copies of lambdaEG10 DNA carrying the gpt gene of E. coli and the red/gam genes of lambda phage are integrated p...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.10152

    authors: Hayashi H,Kondo H,Masumura K,Shindo Y,Nohmi T

    更新日期:2003-01-01 00:00:00

  • Human mutagens: evidence from paternal exposure?

    abstract::The importance of inherited mutations as a cause of human disease has been established clearly through examples of well-defined genetic anomalies, such as Down syndrome and retinoblastoma. Furthermore, it is suspected that environmental contaminants induce mutations resulting in increased risk for such defects in subs...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章,评审

    doi:10.1002/em.2850110311

    authors: Narod SA,Douglas GR,Nestmann ER,Blakey DH

    更新日期:1988-01-01 00:00:00

  • Mitochondrial mutations and human disease.

    abstract::The mitochondrial genome is essential for producing ATP (adenosine 5'-triphosphate) via oxidative phosphorylation. The gradual decline of mitochondrial function with age has long been postulated as a factor in aging. More recently, a variety of diseases have been related to molecular defects in human mitochondrial DNA...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章,评审

    doi:10.1002/em.2850250607

    authors: Grossman LI

    更新日期:1995-01-01 00:00:00