Abstract:
:Transgenic B6C3F1 and C57BL/6 mice containing a lambda shuttle vector that carries a lacI target and an alpha lacZ reporter gene have been constructed for use in in vivo mutagenesis assays. After chemical treatment of mice carrying the lacI target gene, genomic DNA is isolated and the shuttle vector is recovered by exposing the DNA to lambda phage packaging extracts in vitro. Mutations in the lacI target gene that inactivate the repressor gene allow expression of the alpha lacZ reporter gene, resulting in blue mutant plaques. We have examined the ability of two genotoxic agents, dimethylnitrosamine (DMN) and methylmethane sulfonate (MMS), to induce mutations in these transgenic mice. Both compounds induce a variety of DNA adducts in mouse liver; DMN is a hepatocarcinogen that induces significant hepatic cell proliferation, but MMS is not hepatocarcinogenic and does not induce hepatic cell proliferation. The effects of animal age, differences in strain and dosing regimen, and length of expression time were evaluated. Mice were treated for 5, 14 or 21 days and were sacrificed 1, 8 or 22 days after the final dose to evaluate the effects of increased expression time on mutant frequency in liver. In 3 week old mice, DMN (2 mg/kg/day) produced 10- to 20-fold elevations in mutant frequency that increased with expression time and the number of treatments. In contrast, MMS (20 mg/kg/day) failed to increase the mutant frequency. DMN failed to induce mutations in 6 week old mice at 2 mg/kg/day, but 4 mg/kg/day yielded significant elevations in hepatic mutations. Sequencing results indicate that treatment of mice with DMN produced predominantly C:G-->T:A transitions.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Mutagenesisjournal_title
Mutagenesisauthors
Mirsalis JC,Provost GS,Matthews CD,Hamner RT,Schindler JE,O'Loughlin KG,MacGregor JT,Short JMdoi
10.1093/mutage/8.3.265subject
Has Abstractpub_date
1993-05-01 00:00:00pages
265-71issue
3eissn
0267-8357issn
1464-3804journal_volume
8pub_type
杂志文章相关文献
MUTAGENESIS文献大全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 underst...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/ger053
更新日期:2012-01-01 00:00:00
abstract::The mechanism responsible for the modification of mutagenicity by chlorophyllin has been investigated using mutagenic compounds with different mechanisms of action, including the monofunctional alkylating agents, N-methyl-N'-nitrosourea (MNU) and ethylmethanesulphonate (EMS); nitrosamines related to tobacco products, ...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/7.5.349
更新日期:1992-09-01 00:00:00
abstract::Oligodontia, which is the congenital absence of six or more permanent teeth, excluding the third molars, may contribute to masticatory dysfunction, speech alteration, aesthetic problems and malocclusion. Msh homeobox 1 (MSX1) was the first gene identified as causing non-syndromic oligodontia. In this study, we identif...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/geu019
更新日期:2014-09-01 00:00:00
abstract::Despite their prime candidate status, polymorphisms near genes involved in DNA repair or in other functions related to genome stability have been conspicuously under-represented in the significant associations reported from genome-wide association studies (GWAS) of cancer susceptibility. In this study, we assessed a s...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/ger070
更新日期:2012-03-01 00:00:00
abstract::Deregulation of control of the apoptotic process in Fanconi anaemia (FA) appears to be one of the main features of this disease at the cellular level. We show here that FA cells are resistant to treatments with rhodamine-1,2,3 and doxycycline, which both interfere with mitochondrial functionality by different mechanis...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/17.1.25
更新日期:2002-01-01 00:00:00
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
更新日期:2001-11-01 00:00:00
abstract::Aneuploidy has important consequences for human health. There is a requirement to detect aneugens that may not be fully satisfied by the current test batter. New cytogenetic techniques look promising. ...
journal_title:Mutagenesis
pub_type:
doi:10.1093/mutage/13.4.417
更新日期:1998-07-01 00:00:00
abstract::The genotoxicity of atenolol, a beta-blocker antihypertensive drug, both in vitro and in vivo, was cytogenetically tested for its ability to induce sister chromatid exchange (SCE) and micronuclei (MN) in cultured peripheral lymphocytes. Also, fluorescence in situ hybridization (FISH) with a centromeric probe was perfo...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/15.3.195
更新日期:2000-05-01 00:00:00
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
更新日期:1992-01-01 00:00:00
abstract::There are several reports demonstrating that aneugens may preferentially affect segregation of particular chromosomes in somatic cells. Much less is known on specific susceptibility of individual chromosomes to non-disjunction in mammalian meiosis in response to chemical exposures. To explore possible chromosome-speci...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/16.5.407
更新日期:2001-09-01 00:00:00
abstract::The development and use of chromosome-specific DNA probes to label entire human chromosomes has been an important advance in molecular cytogenetics. Fluorescence in situ hybridization using whole chromosome-specific DNA probes has been used to study both numerical and structural chromosomal aberrations in many human c...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/8.3.189
更新日期:1993-05-01 00:00:00
abstract::A perceived disadvantage of transgenic rodent mutation assays is that spontaneous mutant frequencies are high compared to those of endogenous genes and may consequently reduce sensitivity to induced mutation. We have previously argued that unrepaired G:T mismatches from spontaneous deamination of 5-methylcytosine at C...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/gen026
更新日期:2008-09-01 00:00:00
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
更新日期:2003-01-01 00:00:00
abstract::Basic extracts isolated from lamb meat treated at various temperatures were tested for mutagenicity in Salmonella typhimurium strain TA98 in the presence of S9 mix. Samples of ground lamb patties were cooked for 10 min per side at 100, 150, 200, 250 and 300 degrees C. Low cooking temperatures resulted in products with...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/4.3.228
更新日期:1989-05-01 00:00:00
abstract::A spectrum of 100 mutations in the endogenous hprt gene of the human lymphoblastoid TK6 cell line is presented. The majority of the mutations originates in sequences outside the coding region of the gene. Large deletions are a major cause of inactivation of the hprt gene (57% of the mutants). Mutations in the splice s...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/10.2.137
更新日期:1995-03-01 00:00:00
abstract::In order to establish the capacity of Mytilus spp. to form genotoxin-DNA adducts, a series of in vitro and in vivo studies were conducted in which tissue samples and animals were exposed to five model genotoxins. Following the in vitro characterization of the major adducts induced by the compounds, a series of in vivo...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/12.3.153
更新日期:1997-05-01 00:00:00
abstract::Many chemical carcinogens require metabolic activation to form genotoxic compounds in human. Standard in vitro genotoxicity assays performed with activation systems, such as rat liver S9, are recognised to lead to a high number of false positives. The aim of this study was to evaluate the suitability of differentiated...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/geq039
更新日期:2010-11-01 00:00:00
abstract::Alzheimer's disease (AD) is a neurodegenerative disorder of the elderly with a complex etiology due to the interaction between genetic and environmental factors. At least 15% of cases are inherited as an autosomal dominant mutation, but the majority are sporadic. We evaluated cytogenetic alterations, both spontaneous ...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/16.4.323
更新日期:2001-07-01 00:00:00
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
更新日期:2003-11-01 00:00:00
abstract::A working party was set up by the UK Environmental Mutagen Society to consider alternatives to Aroclor 1254 (Aroclor)-induced S9 in in vitro genotoxicity assays, with the aims of considering whether a replacement for Aroclor in its role in general screening assays could be readily identified. The working party conclud...
journal_title:Mutagenesis
pub_type:
doi:10.1093/mutage/7.3.175
更新日期:1992-05-01 00:00:00
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
更新日期:2002-07-01 00:00:00
abstract::The cytokinesis-block micronucleus cytome (CBMNCyt) assay is a widely used technique for measuring DNA damage in human populations. The formation of micronuclei (MN) in dividing cells can result from chromosome breakage due to unrepaired or mis-repaired DNA lesions or chromosome malsegregation due to mitotic malfuncti...
journal_title:Mutagenesis
pub_type: 杂志文章,评审
doi:10.1093/mutage/geq076
更新日期:2011-01-01 00:00:00
abstract::Studies in mono-culture of cells have shown that diesel exhaust particles (DEPs) increase the production of reactive oxygen species (ROS) and oxidative stress-related damage to DNA. However, the level of particle-generated genotoxicity may depend on interplay between different cell types, e.g. lung epithelium and immu...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/ges035
更新日期:2012-11-01 00:00:00
abstract::Polychlorinated biphenyls (PCBs) are stable pollutants, which can be found in almost every compartment of terrestrial and aquatic ecosystems. They are very lipophilic and therefore have the potency of accumulating in the fat stores of animals. The mechanisms by which PCBs exert their adverse effects are still unclear....
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/11.5.485
更新日期:1996-09-01 00:00:00
abstract::In Saccharomyces cerevisiae, disruption of genes by deletion allowed elucidation of the molecular mechanisms of a series of human diseases, such as in Wilson disease (WD). WD is a disorder of copper metabolism, due to inherited mutations in human copper-transporting ATPase (ATP7B). An orthologous gene is present in S....
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/gev062
更新日期:2016-01-01 00:00:00
abstract::The nucleoside analog zidovudine (3'-azido-3'-deoxythymidine, AZT), by itself or in combination with other anti- retroviral drugs, is used perinatally to prevent mother to child transmission of human immunodeficiency virus type 1. AZT is mutagenic in vitro and mutagenic and carcinogenic when administered to neonatal m...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/geh033
更新日期:2004-07-01 00:00:00
abstract::The effects of salts of 27 elements on recombination and on the production of disomic and/or diploid spores during meiosis of Saccharomyces cerevisiae has been investigated. Be(NO3)2, MgSO4, FeSO4, CuSO4, AgNO3, Na2HAsO4 were inactive on the events studied during meiotic cell division. AuCl4, CdCl2, C4H6O4Pb, SnCl2, K...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/1.1.21
更新日期:1986-01-01 00:00:00
abstract::The human JC virus (JCV) is potentially carcinogenic to humans as a Group 2B carcinogen, and it is ubiquitous in human populations. To investigate whether the small tumour (ST) antigen of the JCV contributes to genomic instability, we established cell lines stably expressing the JCV ST and examined its role in DNA rep...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/gev004
更新日期:2015-07-01 00:00:00
abstract::Recent studies suggest increased cancer risk in patients with type 2 diabetes mellitus (T2DM) compared with healthy individuals. The present study aims to assess whether T2DM is associated with increased genome instability and whether a healthy diet with natural foods can improve genome stability in peripheral blood l...
journal_title:Mutagenesis
pub_type: 杂志文章,随机对照试验
doi:10.1093/mutage/ges073
更新日期:2013-03-01 00:00:00
abstract::The mechanistic/mammalian target of rapamycin (mTOR) is a conserved protein kinase that controls several anabolic processes required for cell growth and proliferation. As such, mTOR has been implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes and neurodegeneration....
journal_title:Mutagenesis
pub_type: 杂志文章,评审
doi:10.1093/mutage/geu045
更新日期:2015-03-01 00:00:00