Baseline levels of chromosome instability in the human lymphoblastoid cell TK6.

Abstract:

:Induced genomic instability in the human B lymphoblastoid cell line TK6 manifests itself as increases in end-to-end chromosome fusions and non-reciprocal chromosome translocations. It is not associated with elevated frequencies of specific locus mutations or other cytogenetic alterations. Previous studies on a limited number of cells and end-points suggested that induced instability in TK6 mirrors spontaneous instability in terms of the types of alterations observed. In the present study we expanded on our previous analysis to include more cells and more end-points in order to derive a more precise measure of spontaneous instability in TK6 cells. The frequency of normal growth rate thymidine kinase mutants (TK(-/-)), measured in 44 independently isolated clones, was 2.73 +/- 0.78 x 10(-6)/cell, while that for slow growth mutants was 2.39 +/- 0.52 x 10(-6)/cell. These are similar to the frequencies observed for HPRT mutants in primary human cells. There was wide variation in chromatid break frequencies, but the average break frequency, at 0.04+/-0.01 breaks/cell, was only slightly higher than that reported for primary human cells. In contrast, the dicentric frequency of 0.006/cell was more than 10-fold higher for TK6 cells than that reported for normal primary human cells. Furthermore, the dicentrics in TK6 cells are unusual in that they are the result of end-to-end chromosome fusions. TK6 cells also show much higher levels of non-reciprocal chromosome translocations than are usually observed in primary human cells. The results suggest an inherent instability in TK6 cells that differs from what is observed in primary cells in that it affects the frequency of end-to-end chromosome fusions and non-reciprocal chromosome translocations, but not TK gene mutations or other cytogenetic alterations.

journal_name

Mutagenesis

journal_title

Mutagenesis

authors

Schwartz JL,Jordan R,Evans HH,Lenarczyk M,Liber HL

doi

10.1093/mutage/geh060

subject

Has Abstract

pub_date

2004-11-01 00:00:00

pages

477-82

issue

6

eissn

0267-8357

issn

1464-3804

pii

19/6/477

journal_volume

19

pub_type

杂志文章
  • Effects of the order of exposure to a binary mixture of mutagens on the induced mutation spectra in the supF gene.

    abstract::We have shown previously that UVC irradiation of benzo[a]pyrene diol epoxide (BPDE)-adducted DNA (BPDE/UVC) induces an increase in mutation frequency in the supF gene greater than the calculated additive value derived from either treatment alone, with a greater absolute increase in the level of BPDE signature transver...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/geh011

    authors: McLuckie KI,Gaskell M,Farmer PB,Martin EA,Jones GD,Routledge MN

    更新日期:2004-03-01 00:00:00

  • DNA repair and replication in lymphocytes from smokers exposed in vitro to UV light.

    abstract::In a sample of healthy subjects (23-59 years old), comprising 49 non-smokers and 23 smokers, we studied the effects of smoking on DNA repair synthesis (UDS) in peripheral lymphocytes. DNA repair after UV-irradiation was measured by [3H]TdR incorporation into DNA (semi-conservative synthesis was inhibited by hydroxyure...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/4.2.82

    authors: Celotti L,Furlan D,Ferraro P,Levis AG

    更新日期:1989-03-01 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

  • Meta-analysis of the effect of HHEX gene polymorphism on the risk of type 2 diabetes.

    abstract::In the past decade, a number of case-control studies have been carried out to investigate the relationship between the HHEX polymorphism and type 2 diabetes (T2D). However, the results have been inconclusive. To investigate this inconsistency, we performed a meta-analysis of all available studies dealing with the rela...

    journal_title:Mutagenesis

    pub_type: 杂志文章,meta分析

    doi:10.1093/mutage/geq095

    authors: Cai Y,Yi J,Ma Y,Fu D

    更新日期:2011-03-01 00:00:00

  • Increased translocation frequency of chromosomes 7, 11 and 14 in lymphocytes from patients with neurocysticercosis.

    abstract::Neurocysticercosis (NCC) has been associated with a high frequency of DNA damage in human circulating lymphocytes and more recently with the development of hematological malignancies. Chronic inflammation, a common feature of helminthic infections, has been proposed to play a key role in carcinogenesis induced by para...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/16.6.495

    authors: Herrera LA,Rodríguez U,Gebhart E,Ostrosky-Wegman P

    更新日期:2001-11-01 00:00:00

  • Direct and indirect non-disjunction in the origin of trisomy in cultured human lymphocytes.

    abstract::The aim of the present work was to investigate the processes involved in the origin of trisomic karyotypes, i.e. co-migration of sister chromatids (mitotic non-disjunction, MND) and recovery of micronuclei (MN) originating from lagging chromosomes/chromatids at anaphase (mitotic indirect non-disjunction, MIND), and to...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/14.6.557

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

    更新日期:1999-11-01 00:00:00

  • Involvement of homologous recombination repair after proton-induced DNA damage.

    abstract::Protection from chronic exposure to cosmic radiation, which is primarily composed of protons, in future manned missions to Mars and beyond is considered to be a key unresolved issue. To model the effects of cosmic radiation on a living cell, we used Saccharomyces cerevisiae cells harboring various deletions of DNA rep...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/gem055

    authors: Rostek C,Turner EL,Robbins M,Rightnar S,Xiao W,Obenaus A,Harkness TA

    更新日期:2008-03-01 00:00:00

  • Cobaltous chloride-induced mutagenesis in the supF tRNA gene of Escherichia coli.

    abstract::The spectrum of mutations induced by cobalt(II) chloride (CoCl2) was examined using plasmid pUB3 DNA, which was propagated after transfection into Escherichia coli SY1032/pKY241 host cells. The vector plasmid carried an E.coli supF suppressor tRNA gene as a target for mutations. After CoCl2 treatment, 64 independent n...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/14.2.249

    authors: Ogawa HI,Ohyama Y,Ohsumi Y,Kakimoto K,Kato Y,Shirai Y,Nunoshiba T,Yamamoto K

    更新日期:1999-03-01 00:00:00

  • The Cox-2 -1195 G > A polymorphism and cancer risk: a meta-analysis of 25 case-control studies.

    abstract::Cyclooxygenase 2 (Cox-2, a rate-limiting enzyme in the conversion of arachidonic acid to prostanoids) has been implicated in several physiological and pathological processes, and it has been reported that polymorphisms in the regulatory region of Cox-2 might influence its expression, contributing to the interindividua...

    journal_title:Mutagenesis

    pub_type: 杂志文章,meta分析

    doi:10.1093/mutage/ger040

    authors: Tang Z,Nie ZL,Pan Y,Zhang L,Gao L,Zhang Q,Qu L,He B,Song G,Zhang Y,Shukui Wang

    更新日期:2011-11-01 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

  • Gene mutation and V(D)J recombination in the radiosensitive irs lines.

    abstract::The lines irs1, irs2 and irs3, derived from V79-4 hamster cells, are sensitive to DNA-damaging agents including ionizing radiations. However, unlike some other radiosensitive lines, the irs lines show no apparent defect in the repair of DNA strand breaks. We have now assessed the mis-repair of DNA damage in the irs li...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/9.2.163

    authors: Thacker J,Ganesh AN,Stretch A,Benjamin DM,Zahalsky AJ,Hendrickson EA

    更新日期:1994-03-01 00:00:00

  • Interaction of radiation- and bleomycin-induced lesions and influence of glutathione level on the interaction.

    abstract::Radiation-induced exchange aberrations are thought to arise as a consequence of misrejoining of free ends of DNA double strand breaks (dsbs). In quiescent mammalian cells this process of misrejoining is prevalently taken up by the non-homologous end joining (NHEJ) process. In order to investigate the role of glutathio...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/gei046

    authors: Dutta A,Chakraborty A,Saha A,Ray S,Chatterjee A

    更新日期:2005-09-01 00:00:00

  • Effects of black tea theafulvins on aflatoxin B(1) mutagenesis in the Ames test.

    abstract::Black tea theafulvins, a fraction of thearubigins isolated from black tea aqueous infusions, potentiated the mutagenic activity of the mycotoxin aflatoxin B(1) in the Ames test, in the presence of a hepatic S9 activation system derived from Aroclor 1254-treated rats. In contrast, when the S9 activation system was repl...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/18.2.145

    authors: Catterall F,Copeland E,Clifford MN,Ioannides C

    更新日期:2003-03-01 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

  • Metabolic formation, synthesis and genotoxicity of the N-hydroxy derivative of the food mutagen 2-amino-1-methyl-6-phenylimidazo (4,5-b) pyridine (PhIP).

    abstract::Hepatic microsomes from rats pretreated with PCB were found to metabolize the food mutagen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) to two major metabolites, one of which was identified as the N-hydroxy derivative, 2-hydroxy-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (N-OH-PhIP). This identification w...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/6.1.93

    authors: Frandsen H,Rasmussen ES,Nielsen PA,Farmer P,Dragsted L,Larsen JC

    更新日期:1991-01-01 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

  • Chromosomal localization of human O6-methylguanine-DNA methyltransferase (MGMT) gene by in situ hybridization.

    abstract::Recombinant lambda phage DNA containing segments of human O6-methylguanine-DNA transferase gene was employed to localize this gene among the human chromosomes using non-radioactive in situ hybridization technique. This gene was found to be present at the telomeric end, 26q, of the long arm of the chromosome 10. ...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/7.1.83

    authors: Natarajan AT,Vermeulen S,Darroudi F,Valentine MB,Brent TP,Mitra S,Tano K

    更新日期:1992-01-01 00:00:00

  • Relationships between the DNA adducts and the mutations and sister-chromatid exchanges produced in Chinese hamster ovary cells by N-hydroxy-2-aminofluorene, N-hydroxy-N'-acetylbenzidine and 1-nitrosopyrene.

    abstract::Chinese hamster ovary cells were exposed to N-hydroxy-2-aminofluorene, N-hydroxy-N'-acetylbenzidine and 1-nitrosopyrene, and the resulting DNA adducts, sister-chromatid exchanges (SCEs) and mutations at the hypoxanthine-guanine phosphoribosyl transferase locus were quantified. Each agent produced a major DNA adduct su...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/1.3.201

    authors: Heflich RH,Morris SM,Beranek DT,McGarrity LJ,Chen JJ,Beland FA

    更新日期:1986-05-01 00:00:00

  • The Fanconi anaemia genome stability and tumour suppressor network.

    abstract::Fanconi anaemia (FA) is a rare autosomal recessive disease characterized by increased spontaneous and DNA crosslinker-induced chromosome instability, progressive pancytopenia and cancer susceptibility. An increasing number of genes are involved in FA, including the breast cancer susceptibility gene BRCA2. Five of the ...

    journal_title:Mutagenesis

    pub_type: 杂志文章,评审

    doi:10.1093/mutage/17.6.529

    authors: Bogliolo M,Cabré O,Callén E,Castillo V,Creus A,Marcos R,Surrallés J

    更新日期:2002-11-01 00:00:00

  • Partial pronase digestion of rat gastric mucosa isolates cells undergoing replicative DNA synthesis.

    abstract::A pronase digestion procedure for the isolation of gastric mucosal cells was evaluated for its usefulness in measuring unscheduled DNA synthesis (UDS). The method has been claimed to be suited for assessing the genotoxicity potential of compounds. Compounds were given orally to rats. After 13 h [3H]thymidine was injec...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/6.1.3

    authors: Larsson H,Fryklund J,Helander HF,Wallmark B

    更新日期:1991-01-01 00:00:00

  • Confounding experimental considerations in nanogenotoxicology.

    abstract::The development of novel nanomaterials with unique physico-chemical properties is increasing at a rapid rate, with potential applications across a broad range of manufacturing industries and consumer products. Nanomaterial safety is therefore becoming an increasingly contentious issue that has intensified over the pas...

    journal_title:Mutagenesis

    pub_type: 杂志文章,评审

    doi:10.1093/mutage/gep010

    authors: Doak SH,Griffiths SM,Manshian B,Singh N,Williams PM,Brown AP,Jenkins GJ

    更新日期:2009-07-01 00:00:00

  • Genotoxic potential of crown ethers in Salmonella typhimurium.

    abstract::Macrocyclic polyethers (crown ethers) are a family of compounds which possess the ability to transport ionic species across natural and artificial membranes. Because of this characteristic, they have wide applications in industry and are being investigated for their potential as pharmacologic agents. However, these co...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/4.6.437

    authors: Arenaz P,Bitticks L,Pannell K,Garcia S

    更新日期:1989-11-01 00:00:00

  • Bystander effects induced by chemicals and ionizing radiation: evaluation of changes in gene expression of downstream MAPK targets.

    abstract::Radiation-induced bystander effects have been evaluated extensively, including the involvement of the mitogen-activated protein kinase (MAPK) pathways. However, few studies have examined the ability of chemicals to induce bystander effects, and the molecular mechanisms involved in chemical bystander effects have not b...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/geq003

    authors: Asur R,Balasubramaniam M,Marples B,Thomas RA,Tucker JD

    更新日期:2010-05-01 00:00:00

  • The nature of high frequency sister chromatid exchange cells (HFCs).

    abstract::We employed the three-way differential staining technique (TWD), which allows SCEs to be distinguished on a per generation basis by scoring third metaphases (M3), in order to study the spontaneous levels of SCEs in normal and high frequency cells (HFCs) that occurred in the first (S1), second (S2) and third (S3) S pha...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/12.5.329

    authors: Ponzanelli I,Landi S,Bernacchi F,Barale R

    更新日期:1997-09-01 00:00:00

  • Apoptosis can be a confusing factor in in vitro clastogenic assays.

    abstract::Among the tests used to determine the mutagenic potential of chemicals, the chromosomal aberrations and micronucleus assays play an important role. These tests score either chromosomal structural aberrations at metaphase or micronuclei at interphase. One of the hallmarks of apoptosis is DNA fragmentation into 50-300 k...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/16.3.243

    authors: Meintières S,Biola A,Pallardy M,Marzin D

    更新日期:2001-05-01 00:00:00

  • Extended-term cultures of human T-lymphocytes: a practical alternative to primary human lymphocytes for use in genotoxicity testing.

    abstract::A simplified method, using recombinant interleukin-2, foetal bovine serum and freeze-killed feeder cells, has been developed for the mass culture of T-lymphocytes derived from human peripheral blood. In this protocol, bulk cultures can be cryopreserved approximately 8 days after initiation, and subsequent mass culture...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/10.3.189

    authors: O'Donovan MR,Freemantle MR,Hull G,Bell DA,Arlett CF,Cole J

    更新日期:1995-05-01 00:00:00

  • Repairability during G1 of lesions eliciting sister chromatid exchanges induced by methylmethanesulfonate or ethylmethanesulfonate in bromodeoxyuridine-substituted and unsubstituted DNA strands.

    abstract::The repairability during G(1) of DNA lesions eliciting sister chromatid exchanges (SCE) induced by methylmethanesulfonate (MMS) and ethylmethanesulfonate (EMS) in BrdU-substituted and unsubstituted DNA strands was determined in murine salivary gland cells in vivo. The SCE frequency was determined after exposure to MMS...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/18.1.13

    authors: González-Beltrán F,Morales-Ramírez P

    更新日期:2003-01-01 00:00:00

  • A test of the mutagenicity of cooked meats in vivo.

    abstract::There is a correlation between intestinal cancer and diets high in meat, so fried beef, chicken, lamb, pork and fish were tested for their ability to induce mutations in the small intestine of mice. The mice were bred to be heterozygous at the Dlb-1 locus so that loss of the dominant Dlb-1 b allele by mutation could b...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/16.2.103

    authors: Heddle JA,Knize MG,Dawod D,Zhang XB

    更新日期:2001-03-01 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