Abstract:
:Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are mutagenic and carcinogenic environmental pollutants found in diesel exhaust and on urban air pollution particles. In the present study, human bronchial epithelial BEAS-2B cells were exposed to 2-nitrobenzanthrone (2-NBA) and 3-nitrobenzanthrone (3-NBA). DNA damage responses were compared to those observed after exposure to 1-nitropyrene (1-NP) and benzo[a]pyrene (B[a]P). Examination by microscopy revealed that 3-NBA was the most potent toxic compound while weaker responses were observed with 1-NP and B[a]P. Most interestingly, 2-NBA did not induce cell death or any other stress-related responses. 3-NBA induced a typical apoptotic cell death judged by nuclear condensation and little plasma membrane damage as well as cleavage of caspase 3 and poly-(ADP-ribose) polymerase (PARP). Exposure to 3-NBA resulted in an accumulation of cells in S-phase, and further analysis by Western blotting, immunocytochemistry and flow cytometry revealed that 3-NBA induced a DNA damage response characterized by phosphorylation of ATM (ataxia-telangiectasia mutated), checkpoint kinase (Chk) 2/Chk1, H2AX and p53. The p53 inhibitor pifithrin-α inhibited 3-NBA-induced apoptosis while small effects were seen using pifithrin-μ, suggesting that 3-NBA-induced cell death is a result of transcriptional activation of p53. In conclusion, 3-NBA is a potent inducer of apoptosis, which seemed to be triggered by the DNA damage response. Furthermore, a change of the nitro-group to the second position (i.e. 2-NBA) dramatically changed the cellular reactivity of the compound.
journal_name
Mutagenesisjournal_title
Mutagenesisauthors
Oya E,Ovrevik J,Arlt VM,Nagy E,Phillips DH,Holme JAdoi
10.1093/mutage/ger035subject
Has Abstractpub_date
2011-11-01 00:00:00pages
697-708issue
6eissn
0267-8357issn
1464-3804pii
ger035journal_volume
26pub_type
杂志文章相关文献
MUTAGENESIS文献大全abstract::Nanoremediation of soil, ground and surface water using nanoscale zerovalent iron particles (nZVI) has facilitated their direct environmental exposure posing ecotoxicological concerns. Numerous studies elucidate their phytotoxicity in terms of growth and their fate within the plant system. However, their potential gen...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/gex006
更新日期:2017-05-01 00:00:00
abstract::Recent problems with the supply of Difco bacto agar have forced some laboratories to evaluate alternative agars for use in the Salmonella/microsome assay. This led to the independent observation in two laboratories (Boots and Glaxo) that Salmonella typhimurium TA97a is sensitive to certain types of agar that may be us...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/7.1.13
更新日期:1992-01-01 00:00:00
abstract::o-Phenylphenol (OPP), a widely used fungicide and antibacterial agent, has been considered to be among the top 10 home and garden pesticides used in the USA. Earlier studies have consistently shown that the sodium salt of OPP (SOPP) causes bladder cancer in male Fischer 344 (F344) rats, whereas OPP has produced variab...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/17.1.89
更新日期:2002-01-01 00:00:00
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
更新日期:2007-05-01 00:00:00
abstract::Gaulden reported a novel and unexpected mitomycin C (MMC) effect, namely a pronounced retardation of very late prophase and loss of chromosome orientation in neuroblasts of the grasshopper Chortophaga viridifasciate. Because this effect may be due to interactions of MMC with non-DNA targets, MMC was tested for its int...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/4.1.39
更新日期:1989-01-01 00:00:00
abstract::Over the past several years, we have been evaluating the mutagenicity and clastogenicity of compounds capable of Michael-type reactions. These compounds, including acrylamide, several acrylate and methacrylate esters, vinyl sulfones, and phorone, have been evaluated using TK+/- -3.7.2C mouse lymphoma cells. Mutagenic ...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/6.6.519
更新日期:1991-11-01 00:00:00
abstract::It has been hypothesised that positive associations between age and levels of oxidative stress-generated damage to DNA may be related to an age-dependent decline in DNA repair activity. The objective of this study was to investigate the association between age and repair activity of oxidatively damaged DNA in peripher...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/gev031
更新日期:2015-09-01 00:00:00
abstract::Anaesthetics have gained a lot of attention for their potential mutagenic/carcinogenic effects. In the present study we have investigated the genotoxicity of the inhalation anaesthetic sevoflurane on DNA of lymphocytes isolated from 20 patients undergoing orthopaedic surgery. The genotoxicity of the anaesthetic was st...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/geg013
更新日期:2003-09-01 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::Dibenz[a,h]anthracene (DB[a,h]A) is a polycyclic aromatic hydrocarbon that is a by-product of combustion and a potent carcinogen. Few studies have investigated the effects of DB[a,h]A on mRNA and microRNA expression to dissect the mechanisms involved in carcinogenesis. In this study, mature male mice (Muta(™)Mouse) we...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/get031
更新日期:2013-09-01 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::In order to validate the in vivo micronucleus test in mouse splenocytes using the cytokinesis block method, 14 compounds with various mechanisms of action were tested: three direct alkylating agents (mitomycin C, ethylnitrosourea, beta-propiolactone), seven indirect alkylating agents (cyclophosphamide, benzo[a]pyrene,...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/9.3.199
更新日期:1994-05-01 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::The XPF and ERCC1 proteins form a tight complex and function as an endonuclease to incise on the 5'-side of pyrimidine dimers in DNA. Levels of both proteins are extremely low in group F xeroderma pigmentosum (XP-F) cells. We transfected XP-F cells with the plasmids expressing XPF or ERCC1 and examined levels of both ...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/13.6.595
更新日期:1998-11-01 00:00:00
abstract::The present study was undertaken to compare the antimutagenic activity of aqueous extracts, at the concentrations used for human consumption, from green, black and decaffeinated black tea. Antimutagenic potential was evaluated against three indirect-acting dietary carcinogens, Glu-P-1, benzo(a)pyrene and nitrosopyrrol...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/11.6.597
更新日期:1996-11-01 00:00:00
abstract::The effect of cerium oxide nanoparticle (CeNP) in plants has elicited substantial controversy. While some investigators have reported that CeNP possesses antioxidant properties, others observed CeNP to induce reactive oxygen species (ROS). In spite of considerable research carried out on the effects of CeNP in metazoa...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/gey004
更新日期:2018-04-13 00:00:00
abstract::Implementation of the seventh amendment to the EU Cosmetics Directive has driven much research into suitable in vitro alternative assays to support satisfactory risk assessments. One such assay is the reconstructed skin micronucleus (RSMN) assay. First reported in 2006, further development occurred and a standard prot...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/gez037
更新日期:2019-12-03 00:00:00
abstract::The restriction site mutation method described by Parry et al. (1990) for isolating mutant sequences directly from DNA is discussed and an additional enrichment step proposed using magnetic beads. ...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/5.6.523
更新日期:1990-11-01 00:00:00
abstract::Photomutagenicity assays are required for regulatory submissions of some chemicals. As yet there are no well-validated protocols available for these assays. Critical factors which may contribute to the ability of a bacterial assay to detect photomutagens (e.g. dose of UV and test chemical, exposure conditions, light s...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/9.5.459
更新日期:1994-09-01 00:00:00
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
更新日期:1991-01-01 00:00:00
abstract::The non-syndromic cleft lip and/or palate (NSCL/P) is a common birth defect caused by a combination of genetic and environmental factors. The possible role of genome instability on NSCL/P patient needs more investigation, since DNA metabolism is an essential cellular function to keep cells with normal genotypes and ge...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/gew068
更新日期:2017-03-01 00:00:00
abstract::This study was a part of an international project sponsored by the Commission of the European Communities to evaluate the utility of certain bioassays including hexaploid wheat assay to identify potential aneugens. Ten suspect spindle poisons, i.e. colchicine (COL), cadmium chloride (CdCl2), chloral hydrate (CH), diaz...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/6.5.369
更新日期:1991-09-01 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::Prostate cancer is a major health burden, being the second most commonly diagnosed malignancy in men worldwide. Overtreatment represents a major problem in prostate cancer therapy, leading to significant long-term quality-of-life effects for patients and a broad socio-ecological burden. Biomarkers that could facilitat...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/geaa010
更新日期:2020-07-11 00:00:00
abstract::The presence of an adaptive response to low doses of alkylating chemicals in the phototrophic bacteria Rhodobacter sphaeroides and R.capsulatus has been studied. Results obtained show that both strains display this repair response against the challenge doses of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), when they ar...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/3.2.165
更新日期:1988-03-01 00:00:00
abstract::Due to the very limited transduction capacity of hitherto available vectors, the success of gene therapy of tumours by means of suicide genes has so far essentially depended on the transfer of toxic drug metabolites from transduced (metabolizing) cells to adjacent non-transduced cells via gap junctions (bystander effe...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/geh002
更新日期:2004-01-01 00:00:00
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
更新日期:2001-03-01 00:00:00
abstract::Coal miners are exposed to coal dust, containing mineral particles, inorganic compounds and polycyclic aromatic hydrocarbons, and to ionizing radiation. These factors can induce oxidative stress and promote inflammation that leads to DNA damage. The aim of this investigation is to analyse the degree of DNA damage in m...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/gew038
更新日期:2016-11-01 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::In vivo genotoxicity studies-shortly followed by carcinogenicity-are posing high demand for test-related recourses in terms of animal lives and resources. Among those, the micronucleus test in rodents is the most widely used as a follow-up to positive in vitro mutagenicity results; therefore, the development and exten...
journal_title:Mutagenesis
pub_type: 杂志文章
doi:10.1093/mutage/geq010
更新日期:2010-07-01 00:00:00