Cell transformation assays for prediction of carcinogenic potential: state of the science and future research needs.

Abstract:

:Cell transformation assays (CTAs) have long been proposed as in vitro methods for the identification of potential chemical carcinogens. Despite showing good correlation with rodent bioassay data, concerns over the subjective nature of using morphological criteria for identifying transformed cells and a lack of understanding of the mechanistic basis of the assays has limited their acceptance for regulatory purposes. However, recent drivers to find alternative carcinogenicity assessment methodologies, such as the Seventh Amendment to the EU Cosmetics Directive, have fuelled renewed interest in CTAs. Research is currently ongoing to improve the objectivity of the assays, reveal the underlying molecular changes leading to transformation and explore the use of novel cell types. The UK NC3Rs held an international workshop in November 2010 to review the current state of the art in this field and provide directions for future research. This paper outlines the key points highlighted at this meeting.

journal_name

Mutagenesis

journal_title

Mutagenesis

authors

Creton S,Aardema MJ,Carmichael PL,Harvey JS,Martin FL,Newbold RF,O'Donovan MR,Pant K,Poth A,Sakai A,Sasaki K,Scott AD,Schechtman LM,Shen RR,Tanaka N,Yasaei H

doi

10.1093/mutage/ger053

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

93-101

issue

1

eissn

0267-8357

issn

1464-3804

pii

ger053

journal_volume

27

pub_type

杂志文章
  • An aphidicolin-block nucleotide excision repair assay measuring DNA incision and repair capacity.

    abstract::The objective of the present study was to develop a cellular phenotype assay for nucleotide excision repair (NER), using benzo[a]pyrene diol epoxide (BPDE) as model mutagen. Since in vitro exposure to BPDE may lead to DNA strand breaks resulting from both direct interaction with DNA and incisions introduced by the rep...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/gep039

    authors: Vande Loock K,Decordier I,Ciardelli R,Haumont D,Kirsch-Volders M

    更新日期:2010-01-01 00:00:00

  • Dietary sugars and related endogenous advanced glycation end-products increase chromosomal DNA damage in WIL2-NS cells, measured using cytokinesis-block micronucleus cytome assay.

    abstract::This study investigated the effect of glucose and fructose, and advanced glycation end-products (AGEs) on genome damage in WIL2-NS cells, measured using the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The effect of AGEs was investigated using the bovine serum albumin (AGE-BSA) model system induced either w...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/geaa002

    authors: Deo P,McCullough CL,Almond T,Jaunay EL,Donnellan L,Dhillon VS,Fenech M

    更新日期:2020-03-27 00:00:00

  • Different mechanisms of reversion of HPRT-deficient V79 Chinese hamster cells.

    abstract::The revertibility of three spontaneous hypoxanthine phosphoribosyl transferase (HPRT)-deficient V79 cell lines has been determined after exposure to a number of alkylating agents. TG11 and 19 reverted at frequencies ranging from 1 X 10(-5) to 1 X 10(-4) after exposure to doses of ethylmethane sulphonate (EMS) N-methyl...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/3.1.15

    authors: Fox M,Rossiter BJ,Brennand J

    更新日期:1988-01-01 00:00:00

  • Is habitual alcohol drinking associated with reduced electrophoretic DNA migration in peripheral blood leukocytes from ALDH2-deficient male Japanese?

    abstract::Alcohol drinking-derived acetaldehyde is believed to cross-link DNA and induce sister chromatid exchanges in peripheral blood lymphocytes. However, little population data are available to illustrate effects of alcohol-derived acetaldehyde on DNA migration as assayed by the comet assay in peripheral lymphocytes. In the...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/gep008

    authors: Lu Y,Morimoto K

    更新日期:2009-07-01 00:00:00

  • The mutagenic potential of non-homologous end joining in the absence of the NHEJ core factors Ku70/80, DNA-PKcs and XRCC4-LigIV.

    abstract::Non-homologous end joining (NHEJ), the major pathway of double-strand break (DSB) repair in mammalian cells, comprises two subpathways: one that requires the three core factors Ku70/80, DNA-PKcs and XRCC4/LigIV (DNA-PK-dependent NHEJ) and the other that is independent of these factors. Using a cell-free NHEJ assay, we...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/gem007

    authors: Kuhfittig-Kulle S,Feldmann E,Odersky A,Kuliczkowska A,Goedecke W,Eggert A,Pfeiffer P

    更新日期:2007-05-01 00:00:00

  • Mutagenicity studies on FD&C red No.3.

    abstract::FD&C Red No.3 (erythrosine) has been used as a dye in foods, drugs and cosmetics since its approval by the US Department of Agriculture in 1907. In 1977 the Certified Color Manufacturers' Association (CCMA) initiated studies on FD&C Red No.3 including chronic toxicity and carcinogenicity studies in rats and mice. Data...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/1.4.253

    authors: Lin GH,Brusick DJ

    更新日期:1986-07-01 00:00:00

  • High-throughput comet assay using 96 minigels.

    abstract::The single-cell gel electrophoresis--the comet assay--has proved to be a sensitive and relatively simple method that is much used in research for the analysis of specific types of DNA damage, and its use in genotoxicity testing is increasing. The efficiency of the comet assay, in terms of number of samples processed p...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/get012

    authors: Gutzkow KB,Langleite TM,Meier S,Graupner A,Collins AR,Brunborg G

    更新日期:2013-05-01 00:00:00

  • Extrapolation of in vitro structural alerts for mutagenicity to the in vivo endpoint.

    abstract::As part of the hazard and risk assessment of chemicals in man, it is important to assess the ability of a chemical to induce mutations in vivo. Because of the commonalities in the molecular initiating event, mutagenicity in vitro can correlate well to the in vivo endpoint for certain compound classes; however, the dif...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/gey030

    authors: Tennant RE,Guesné SJ,Canipa S,Cayley A,Drewe WC,Honma M,Masumura K,Morita T,Stalford SA,Williams RV

    更新日期:2019-03-06 00:00:00

  • Requirements for DNA bubble structure for efficient cleavage by helix-two-turn-helix DNA glycosylases.

    abstract::Oxidative DNA lesions, constantly generated by both endogenous and environmentally induced reactive oxygen species, are removed via the base excision repair pathway. In bacteria, Fpg and Nei DNA glycosylases, belonging to the helix-two-turn-helix (H2TH) structural superfamily, remove oxidised purines and pyrimidines, ...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/gez047

    authors: Makasheva KA,Endutkin AV,Zharkov DO

    更新日期:2020-02-13 00:00:00

  • Detection of the centromere in micronuclei by fluorescence in situ hybridization: its application to the human lymphocyte micronucleus assay after treatment with four suspected aneugens.

    abstract::The human lymphocyte micronucleus (MN) test combined with fluorescence in situ hybridization (FISH) of a centromeric probe is considered a useful screening assay to distinguish between clastogenic and aneugenic agents. Four suspected aneuploidy-inducing chemicals, acetaldehyde (AA), diethylstilbestrol (DES), diethylst...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/11.3.285

    authors: Migliore L,Cocchi L,Scarpato R

    更新日期:1996-05-01 00:00:00

  • Tripterygium hypoglaucum (level) Hutch induces aneuploidy of chromosome 8 in mouse bone marrow cells and sperm.

    abstract::Aneuploidy of mouse chromosome 8 induced by a Chinese medicinal herb, Tripterygium hypoglaucum (level) Hutch (THH) was investigated by fluorescence in situ hybridization (FISH) in vivo. Male mice were treated with THH (single i.p. injection) at doses of 120, 240 and 480 mg/kg. Colchicine (COL, 1.5 mg/kg i.p.) was used...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/geh044

    authors: Xu W,Ziqing L,Yinrun D,Xiaoyan W,Jinglun X

    更新日期:2004-09-01 00:00:00

  • Vitamins at physiological levels cause oxidation to the DNA nucleoside deoxyguanosine and to DNA--alone or in synergism with metals.

    abstract::Vitamins with antioxidant properties have the ability to act as pro-oxidants, inducing oxidative damage and oxidative stress as opposed to preventing it. While vitamin supplements are commonly consumed, the scientific evidence for their health beneficial effects is inconclusive. In fact, even harmful effects have been...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/ges013

    authors: Bergström T,Ersson C,Bergman J,Möller L

    更新日期:2012-07-01 00:00:00

  • Inter-individual variation in the mutagenic activation of 2-acetylaminofluorene by human liver in relation to animal metabolic models.

    abstract::A relatively large, reproducible inter-individual variation was found in the ability of 17 human liver S9 samples to mediate the mutagenicity of 2-acetylaminofluorene (2AAF) in Salmonella typhimurium strain TA98. In an animal model, variation in metabolic activation of 2AAF did not appear to relate to the phenotype of...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/3.4.323

    authors: Smith AJ,Chipman JK

    更新日期:1988-07-01 00:00:00

  • Resistance to the antibiotic Zeocin by stable expression of the Sh ble gene does not fully suppress Zeocin-induced DNA cleavage in human cells.

    abstract::Zeocin is a member of the bleomycin/phleomycin family of antibiotics, known to bind and cleave DNA. We established human SK-OV-3 cells that stably express the Zeocin resistance gene (Sh ble) using an ecdysone-inducible mammalian expression system. Surprisingly, our results demonstrated that Zeocin, added in the cultur...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/gei016

    authors: Oliva-Trastoy M,Defais M,Larminat F

    更新日期:2005-03-01 00:00:00

  • Effect of cytochalasin B on the induction of chromosome missegregation by colchicine at low concentrations in human lymphocytes.

    abstract::The aim of the present work was to investigate the possible interference of cytochalasin B (cyt B) with low concentration treatment with colchicine in the induction of chromosome/chromatid loss and micronuclei in human lymphocytes mitotically activated in vitro. Thus, cells from a single female donor were treated with...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/14.1.43

    authors: Minissi S,Gustavino B,Degrassi F,Tanzarella C,Rizzoni M

    更新日期:1999-01-01 00:00:00

  • Impact of molecular alterations of BRAF in the pathogenesis of thyroid cancer.

    abstract::BRAF alterations represent a novel indicator of the progression and aggressiveness of thyroid carcinogenesis. So, the main aim of the study was to elucidate the involvement of BRAF gene mutations and its expression in Kashmiri (North India) patients and investigate their association with clinico-pathological character...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/get066

    authors: Khan MS,Pandith AA,Azad N,Hussain MU,Masoodi SR,Wani KA,Andrabi KI,Mudassar S

    更新日期:2014-03-01 00:00:00

  • Haemoglobin adducts as biomarkers of occupational exposure to 1,3-butadiene.

    abstract::Adducts of 1,2-epoxy-3-butene (EB) with haemoglobin were monitored in 17 workers from the 1,3-butadiene (BD) production unit of a petrochemical plant and in nine referents employed at the same factory but not exposed to BD. The air concentrations of BD were determined using stationary and personal monitoring. The ambi...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/11.2.145

    authors: Osterman-Golkar S,Peltonen K,Anttinen-Klemetti T,Landin HH,Zorcec V,Sorsa M

    更新日期:1996-03-01 00:00:00

  • Evidence for genotoxicity of pesticides in pesticide applicators: a review.

    abstract::A systematic review of the literature has been conducted and studies reporting investigations of genotoxicity biomarkers in pesticide workers have been assessed with view to establishing whether there was evidence for any risk to those using pesticides approved in the United Kingdom. Each of the studies was evaluated ...

    journal_title:Mutagenesis

    pub_type: 杂志文章,评审

    doi:10.1093/mutage/gel011

    authors: Bull S,Fletcher K,Boobis AR,Battershill JM

    更新日期:2006-03-01 00:00:00

  • Induction and time-dependent accumulation of micronuclei in peripheral blood of transgenic p53+/- mice, Tg.AC (v-Ha-ras) and parental wild-type (C57BL/6 and FVB/N) mice exposed to benzene by inhalation.

    abstract::In this study, we determined the induction and time-dependent accumulation of micronuclei in the peripheral blood of transgenic C57BL/6 p53+/- mice (p53+/- mice), FVB/N Tg.AC v-Ha-ras mice (Tg.AC mice) and their isogenic parental strains, FVB/N and C57BL/6 following inhalation exposure to benzene. Our objective was to...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/16.2.163

    authors: Healy LN,Pluta LJ,James RA,Janszen DB,Torous D,French JE,Recio L

    更新日期:2001-03-01 00:00:00

  • Dose-effect relationships of nucleoplasmic bridges and complex nuclear anomalies in human peripheral lymphocytes exposed to 60Co γ-rays at a relatively low dose.

    abstract::The dose effect between nucleoplasmic bridges (NPB) and relatively low doses of ionising radiation remains unknown. Accordingly, this study investigated the NPB frequencies in human peripheral blood lymphocytes exposed to low-dose (60)Co γ-rays. Complex anomalies, including fused nuclei (FUS), horse-shoe nuclei (HS) a...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/gew001

    authors: Tian XL,Zhao H,Cai TJ,Lu X,Chen DQ,Li S,Liu QJ

    更新日期:2016-07-01 00:00:00

  • Absence of evidence for mutagenicity of alcoholic beverages: an analysis of hprt mutant frequencies in 153 normal humans.

    abstract::A substantial database on hprt mutant frequency in circulating T-cells derived from 153 normal humans was analysed to determine if any effect of alcohol consumption could be detected. Alcohol intake (as reported in a questionnaire completed at the time of the blood sample) ranged from 0 to 35+ units per week. Donors w...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/10.5.449

    authors: Cole J,Green MH

    更新日期:1995-09-01 00:00:00

  • Microwell mutation assays: evaluation of ethylmethanesulphonate, benzo[a]pyrene and benzidine using the tk locus in L5178Y mouse lymphoma cells.

    abstract::As part of the third UKEMS collaborative trial, ICI Central Toxicology Laboratory (CTL) tested the three study chemicals ethylmethanesulphonate (EMS), benzo[a]pyrene (B[a]P) and benzidine (BZD) in a microwell adaptation of the L5178Y gene mutation assay using the thymidine kinase (tk) locus. Cofactors for metabolic ac...

    journal_title:Mutagenesis

    pub_type: 临床试验,杂志文章,多中心研究

    doi:

    authors: Clay P,Cross MF

    更新日期:1990-01-01 00:00:00

  • Bacterial genotoxicity of nitrosated famotidine.

    abstract::Famotidine, a histamine H2-receptor antagonist, was devoid of mutagenic activity in seven his- Salmonella typhimurium strains (TA1535, TA1537, TA1538, TA97, TA98, TA100 and TA102) and was equitoxic in repair-proficient (WP2) and repair-deficient (WP2uvrA, WP67, CM561, CM571, WP100 and CM871) Escherichia coli strains, ...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/1.2.125

    authors: De Flora S,Camoirano A,Basso C,Astengo M,Zanacchi P,Bennicelli C

    更新日期:1986-03-01 00:00:00

  • Detection of nitro-azabenzo[a]pyrene derivatives in the semivolatile phase originating from airborne particulate matter, diesel and gasoline vehicles.

    abstract::Mutagens in the semivolatile phase of airborne particulate matter, diesel and gasoline engine emissions were investigated using chemical and biological assays. The previously unknown mutagens, 1-(3-)nitro-6-azabenzo[a]pyrenes (1-N-6-ABP and 3-N-6-ABP) and 1-(3-)nitro-6-azabenzo[a]pyrene-N-oxides (1-N-6-ABPO and 3-N-6-...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/9.1.47

    authors: Sera N,Fukuhara K,Miyata N,Tokiwa H

    更新日期:1994-01-01 00:00:00

  • Maternal gene polymorphisms involved in folate metabolism and the risk of having a Down syndrome offspring: a meta-analysis.

    abstract::Down syndrome (DS) is the most common chromosomal abnormality. Many studies have assessed the association between maternal gene polymorphisms involved in folate metabolism and the risk of having a DS offspring, but data are conflicting. Our study aimed to arrive at a more accurate estimation. Therefore, we carried out...

    journal_title:Mutagenesis

    pub_type: 杂志文章,meta分析

    doi:10.1093/mutage/get045

    authors: Yang M,Gong T,Lin X,Qi L,Guo Y,Cao Z,Shen M,Du Y

    更新日期:2013-11-01 00:00:00

  • Cytokinesis-block micronucleus assay in primary human liver fibroblasts exposed to griseofulvin and mitomycin C.

    abstract::Primary liver fibroblasts were applied in a cytokinesis-block micronucleus assay in combination with fluorescence in situ hybridization (FISH) using two protocols. In protocol A (Prot. A), cytochalasin B (Cyt B) was added at the end of the treatment time directly to the medium containing the standard compounds, wherea...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/15.2.143

    authors: Nesti C,Trippi F,Scarpato R,Migliore L,Turchi G

    更新日期:2000-03-01 00:00:00

  • Combined treatment with 4-(N-methyl-N-nitrosamino)-1- (3-pyridyl)-1-butanone and dibutyl phthalate enhances ozone-induced genotoxicity in B6C3F1 mice.

    abstract::Potential toxicological interactions of 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and/or dibutyl phthalate (DBP) with ozone were investigated. Male and female B6C3F1 mice were exposed to ozone (0.5 p.p.m.), NNK (1.0 mg/kg), DBP (5000 p.p.m.) and different combinations of these toxicants 6 h/day for 16,...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/17.4.331

    authors: Kim MY,Kim YC,Cho MH

    更新日期:2002-07-01 00:00:00

  • Analysis by fluorescence in situ hybridization with a mouse gamma satellite DNA probe of isolated micronuclei induced in mice by two clastogens and two spindle poisons.

    abstract::The presence of centromeric DNA was studied in micronuclei isolated from the blood of male ddY mice after five weekly intraperitoneal injections of mitomycin C (MMC), 1-beta-D-arabinofuranosylcytosine (Ara-C), colchicine (COL) or vinblastine sulfate (VBL). In agreement with our earlier findings, about half of the micr...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/10.6.513

    authors: Mäki-Paakkanen J,Hayashi M,Suzuki T,Tanabe H,Honma M,Sofuni T

    更新日期:1995-11-01 00:00:00

  • A new cytogenetic approach for the evaluation of mutagenic potential of chemicals that induce cell cycle arrest in the G2 phase.

    abstract::The aim of the present study was to develop and standardize a cytogenetic approach for evaluation of the mutagenic potential of chemicals that induce cell cycle arrest in the G2 phase. Even though cytogenetic end-points such as sister chromatid exchange (SCE) have been extensively used to indirectly assess the DNA-dam...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/geg034

    authors: Terzoudi GI,Malik SI,Pantelias GE,Margaritis K,Manola K,Makropoulos W

    更新日期:2003-11-01 00:00:00

  • Micronucleus morphology as a means to distinguish aneugens and clastogens in the mouse bone marrow micronucleus assay.

    abstract::Detailed dose-response data for two reference aneugens, vincristine and nocodazole, have been derived for the mouse bone marrow micronucleus assay. Positive data have also been described for six other micronucleus-inducing agents: cyclophosphamide; aniline; urethane; 1,2-dimethylhydrazine; 7,12-dimethylbenzanthracene ...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/6.3.193

    authors: Tinwell H,Ashby J

    更新日期:1991-05-01 00:00:00