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, which detects a wide mutational spectrum, ranging from point mutations to LOH-type mutations. TK6, a human lymphoblastoid cell line, is heterozygous for the thymidine kinase (TK) gene and has a wild-type p53 gene. The related cell lines, TK6-E6 and WTK-1, which are p53-deficient and p53-mutant (Ile237), respectively, are also heterozygous for the TK gene and LOH-type mutation can be detected in these cells. Therefore, comparative studies of TK mutation frequency and spectrum with these cell lines are useful for elucidating the role of p53 in generating LOH and maintaining genomic stability in human cells. We demonstrate here that LOH and its associated genomic instability strongly depend on the p53 status in these cells. TK6-E6 and WTK-1 are defective in the G1/S checkpoint and in apoptosis. Unrepaired DSBs that escape from the checkpoint can potentially initiate genomic instability after DNA replication, resulting in LOH and a variety of chromosome changes. Moreover, genomic instability is enhanced in WTK-1 cells. It is likely that the mutant p53 protein in WTK-1 cells increases LOH in a dominant-negative manner due to its abnormal recombination capacity. We discuss the mutator phenotype and genomic instability associated with p53 inactivation with the goal of elucidating the mechanisms of mutation and DNA repair in untargeted mutagenesis.
journal_name
Environ Mol Mutagenjournal_title
Environmental and molecular mutagenesisauthors
Honma Mdoi
10.1002/em.20113subject
Has Abstractpub_date
2005-03-01 00:00:00pages
162-76issue
2-3eissn
0893-6692issn
1098-2280journal_volume
45pub_type
杂志文章,评审abstract::The induction and nature of mutations in the lacI transgene were evaluated in multiple tissues after exposure of adult male B6C3F1 lacI transgenic mice to cyclophosphamide (CP). Mice were given a single i.p. injection of 25 mg CP/kg, 100 mg CP/kg, or vehicle (PBS) and then necropsied 6 weeks after treatment to allow D...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
abstract::We review our studies on the role of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in breast cancer. Additionally we report on analyses of the reliability of the scoring procedures used with immunohistochemical assay for PAH-DNA adducts and of potential bias arising from the use of benign breast disease (BBD) cont...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.10048
更新日期:2002-01-01 00:00:00
abstract::An automated approach for scoring in vitro micronuclei (MN) has been described in which flow cytometric analysis is combined with compound exposure, processing, and sampling in a single 96-well plate (Bryce SM et al. [2010]: Mutat Res 703:191-199). The current report describes protocol optimization and an interlaborat...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21760
更新日期:2013-04-01 00:00:00
abstract::Aldehydes are widespread environmental and industrial compounds, able to stimulate a range of adverse health effects (e.g., general toxicity, allergenic reactions, mutagenicity, and carcinogenicity). We have previously presented quantitative structure-activity relationships (QSARs) for the genotoxicity of simple and a...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20158
更新日期:2005-12-01 00:00:00
abstract::Treatment of AS52 cells with 5-azacytidine resulted in an induction of 6-thioguanine-resistant [6TG] colonies, which reached a maximum by an expression time of 9 days. Dose responses for both cytotoxicity and mutation induction were determined following treatment with 5-azacytidine. At 20 microM treatment, 5-azacytidi...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2280(1996)28:2<100::AID-EM5>3.0
更新日期:1996-01-01 00:00:00
abstract::Human sulfotransferase (SULT) 1A1, 1A2, and 1A3 cDNA genes were subcloned separately into the pTrc99A(KM) vector. The generated plasmids were introduced into the Salmonella typhimurium O-acetyltransferase-deficient strain NM6000 (TA1538/1,8-DNP/pSK1002), resulting in the new strains NM7001, NM7002, and NM7003. We comp...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20696
更新日期:2012-03-01 00:00:00
abstract::Nitrous acid (NA) is often presumed to cause base substitutions in organisms with double-stranded DNA as a direct consequence of oxidative deamination of adenine and of cytosine residues. Here we summarize evidence indicating that other mechanisms are involved in the case of NA-induced G/C-->A/T transition mutations. ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850240305
更新日期:1994-01-01 00:00:00
abstract::Umu test is one of the in vitro genotoxicity test that has been used widely. It was developed as a high-throughput test system using the 96-well microplate. We have previously constructed new umu test strains for the evaluation of genotoxicity of procarcinogenic metabolic products formed by cytochrome P450 (CYP) enzym...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22092
更新日期:2017-05-01 00:00:00
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
更新日期:1988-01-01 00:00:00
abstract::Animal studies have linked perinatal bisphenol A (BPA) exposure to altered DNA methylation, but little attention is given to analyzing multiple physiologically relevant doses. Utilizing the viable yellow agouti (A(vy)) mouse, we examine the effects of developmental exposure through maternal diet to 50 ng BPA/kg (n = 1...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21692
更新日期:2012-06-01 00:00:00
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.
更新日期:1996-01-01 00:00:00
abstract::A collaborative international trial was conducted to evaluate the reproducibility and transferability of an in vivo mutation assay based on the enumeration of CD59-negative rat erythrocytes, a phenotype that is indicative of Pig-a gene mutation. Fourteen laboratories participated in this study, where anti-CD59-PE, SYT...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20672
更新日期:2011-12-01 00:00:00
abstract::Bhawalpur is a major cotton-growing area in Pakistan. Cotton picking in Pakistan is carried out by females and as a result of the intensive use of pesticides during the growing season these females are exposed to pesticide residues in the picking season. In the present study, peripheral blood was obtained from 69 cott...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20395
更新日期:2008-06-01 00:00:00
abstract::A transplacental carcinogenicity study was conducted by exposing pregnant Swiss (CD-1) mice to 0, 50, 100, 200, or 300 mg 3'-azido-3'-deoxythymidine (AZT)/kg body weight (BW) daily for the duration of gestation (18-19 days) [National Toxicology Program,2006]. The incidence of alveolar/bronchiolar adenomas and carcinom...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20420
更新日期:2008-12-01 00:00:00
abstract::Cultured rodent and human cells typically display similar clonal survival characteristics following exposure to ultraviolet light (UV). However, compared to human cells, cultured cells from mice, rats, and hamsters are generally deficient in excision repair of the most prominent DNA lesion produced by UV, the cyclobut...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,评审
doi:10.1002/em.1057
更新日期:2001-01-01 00:00:00
abstract::N-Hydroxymethylacrylamide (NHMA), a mouse carcinogen inactive in the Salmonella assay and mouse micronucleus (MN) assay, was tested for reproductive effects in a mouse continuous breeding study. In that study, increased embryonic deaths were observed after 13 weeks exposure of parental animals to NHMA via drinking wat...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.10139
更新日期:2003-01-01 00:00:00
abstract::Azidothymidine (AZT) is a nucleoside reverse transcriptase inhibitor (NRTI) that is used for reducing mother-to-child transmission of human immunodeficiency virus I. Combinations of AZT and 3'-thiacytidine (3TC) are even more effective than AZT alone. AZT, however, is a mutagen and carcinogen in rodent models and 3TC ...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.20280
更新日期:2007-04-01 00:00:00
abstract::The effects of long-term smoking on mitochondrial DNA (mtDNA) deletions in hair follicles were investigated in subjects with different antioxidant capacity. Twenty-two male smokers with a smoking index of greater than 5 pack-years and without any known systemic diseases were recruited for this study. Forty healthy non...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.10105
更新日期:2002-01-01 00:00:00
abstract::Comparison of spontaneous mutation spectra derived from different transgenic constructs can provide valuable insights for interpreting the mechanisms of spontaneous mutation. In this study, spontaneous mutation frequencies and spectra of the lacI transgene are compared in the liver of C57BL/6, B6C3F1, and BC-1 mice an...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.1021
更新日期:2001-01-01 00:00:00
abstract::The DNA repair proteins XPD and XRCC1 are involved in the nucleotide and base excision repair of DNA lesions induced by many tobacco and environmental carcinogens. Common variant alleles at the XPD (312Asn, 751Gln) and XRCC1 (399Gln) loci have been identified and associated with increased risk for lung cancer. We ther...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.10128
更新日期:2003-01-01 00:00:00
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
更新日期:2001-01-01 00:00:00
abstract::Phosphine is an important fumigant in the grain industry and has been reported to be genotoxic in occupationally exposed fumigators. This study reports on the effects of phosphine inhalation exposure at up to, and exceeding, occupational relevant levels in a subchronic (0.3, 1.0 and 4.5 ppm, 13 weeks) and a short term...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850240202
更新日期:1994-01-01 00:00:00
abstract::The mutational spectrum for 28 X-ray induced mutations and 2 spontaneous mutations, previously determined by genetic and cytogenetic methods, consisted of 20 multilocus deficiencies (19 induced and 1 spontaneous) and 10 intragenic mutations (9 induced and 1 spontaneous). One of the X-ray induced intragenic mutations w...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.2850180303
更新日期:1991-01-01 00:00:00
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
更新日期:1991-01-01 00:00:00
abstract::The 1960s witnessed detailed studies on the genetic properties of a large number of histidine-requiring mutants of Salmonella typhimurium. The early 1970s saw development of selected strains, the Ames strains, for use in rapid, cheap, sensitive, and manipulable tests of chemicals and chemical mixtures for genotoxic ac...
journal_title:Environmental and molecular mutagenesis
pub_type: 历史文章,杂志文章
doi:10.1002/em.2850140610
更新日期:1989-01-01 00:00:00
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
更新日期:2003-01-01 00:00:00
abstract::Micronucleus (MN) expression in peripheral blood lymphocytes is well established as a standard method for monitoring chromosome damage in human populations. The first results of an analysis of pooled data from laboratories using the cytokinesis-block micronucleus (CBMN) assay and participating in the HUMN (HUman Micro...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章,多中心研究
doi:
更新日期:2001-01-01 00:00:00
abstract::Molindone hydrochloride is a dihydroindolone neuroleptic with dopamine D2 and D5 receptor antagonist activity. As an integral component of its preclinical safety evaluation, molindone hydrochloride was evaluated in a series of in vitro and in vivo genetic toxicology assays. In the bacterial reverse gene mutation assay...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.22007
更新日期:2016-05-01 00:00:00
abstract::Coal is the largest fossil fuel source used for the generation of energy. However, coal extraction and its use constitute important pollution factors; thus, risk characterization and estimation are extremely important for the safety of coal workers and the environment. Candiota is located to the southeast of the state...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21744
更新日期:2013-01-01 00:00:00
abstract::Exposure to high concentrations of hexavalent chromium [Cr(VI)] in drinking water was associated with an increased incidence of oral tumors in F344 rats in a 2-year cancer bioassay conducted by the National Toxicology Program. These tumors primarily occurred at 180 ppm Cr(VI) and appeared to originate from the gingiva...
journal_title:Environmental and molecular mutagenesis
pub_type: 杂志文章
doi:10.1002/em.21952
更新日期:2015-08-01 00:00:00