Cytosine arabinoside enhancement of gamma irradiation induced mutations in human T-lymphocytes.

Abstract:

:The frequency of 6-thioguanine resistant (TGr) mutants induced in human G0 phase T-lymphocytes by 200 cGy of gamma irradiation is greatly enhanced by incubation with cytosine arabinoside (ara-C) after irradiation. The mutant frequency increased with increasing incubation time in ara-C for up to 2 hr. This mutation induction required a phenotypic expression time of 5-8 days mass culture growth, similar to that found with mutants induced by 300 cGy of irradiation alone. Southern blot analysis of 40 isolated mutant clones revealed 8 independent mutations by T-cell receptor (TCR) gene rearrangement patterns. Four of these eight showed hprt gene structural alterations (0.50). An alternative method to allow phenotypic expression was developed to minimize the isolation of hprt/TCR sibling mutants. The use of in situ expression in the microtiter dish wells resulted in the isolation of 17 independent mutations in 19 mutant clones. Ten of these 17 mutations showed hprt structural alterations (0.59). The high fraction of mutations involving structural alterations detected by Southern blot analysis is consistent with the known induction of chromosome aberrations by irradiation plus ara-C treatment. We propose that both the increase in Mf and the increase in the incidence of hprt gene structural alterations are due to the accumulation of strand breaks in repairing regions of DNA under these conditions of ara-C induced inhibition of repair. We further propose that upon release of the ara-C inhibition, these repairing regions can interact to yield both gene mutations and chromosome aberrations.

journal_name

Environ Mol Mutagen

authors

O'Neill JP,Sullivan LM,Hunter TC,Nicklas JA

doi

10.1002/em.2850170403

subject

Has Abstract

pub_date

1991-01-01 00:00:00

pages

231-7

issue

4

eissn

0893-6692

issn

1098-2280

journal_volume

17

pub_type

杂志文章
  • Germ cell mutagens: risk assessment challenges in the 21st century.

    abstract::Heritable mutations may result in a wide variety of detrimental outcomes, from embryonic lethality to genetic disease in the offspring. Despite this, today's commonly used test batteries do not include assays for germ cell mutation. Current challenges include a lack of practical assays and concrete evidence for human ...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 历史文章,杂志文章,评审

    doi:10.1002/em.20613

    authors: Singer TM,Yauk CL

    更新日期:2010-10-01 00:00:00

  • Modulatory effects of Mentha piperita on lung tumor incidence, genotoxicity, and oxidative stress in benzo[a]pyrene-treated Swiss albino mice.

    abstract::Mentha piperita or peppermint is currently used for alleviating nausea, flatulence, and vomiting. In the present investigation, we evaluated the chemopreventive, antigenotoxic, and antioxidative effects of an aqueous extract of Mentha piperita leaves. One-day-old Swiss albino mice were treated with a single subcutaneo...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章,收录出版

    doi:10.1002/em.20185

    authors: Samarth RM,Panwar M,Kumar A

    更新日期:2006-04-01 00:00:00

  • Antimutagenicity of a low molecular weight superoxide dismutase mimic against oxidative mutagens.

    abstract::A set of stable nitroxide free radicals that are used as spin labels have been shown to possess metal-independent superoxide dismutase-like activity. Unlike superoxide dismutase (SOD), these compounds are low molecular weight, and readily penetrate into the cell. A representative nitroxide, 4-hydroxy-2,2,6,6-tetrameth...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.2850190105

    authors: DeGraff WG,Krishna MC,Russo A,Mitchell JB

    更新日期:1992-01-01 00:00:00

  • Aurora A, centrosome structure, and the centrosome cycle.

    abstract::The centrosome, also known as the microtubule organizing center of the cell, is a membrane-less organelle composed of a pair of barrel-shaped centrioles surrounded by electron-dense pericentriolar material. The centrosome progresses through the centrosome cycle in step with the cell cycle such that centrosomes are dup...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章,评审

    doi:10.1002/em.20533

    authors: Lukasiewicz KB,Lingle WL

    更新日期:2009-10-01 00:00:00

  • Mutational spectra in transgenic animal research: data analysis and study design based upon the mutant or mutation frequency.

    abstract::Understanding chemically induced changes in mutational spectra can aid in deciphering mechanisms of mutagenesis. In this paper, we propose the use of statistical methods that are based upon the mutation frequency, rather than simple mutant counts which have no relationship to the mutation frequency. These methods have...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2280(1996)28:4<405::AID-EM15>3.

    authors: Carr GJ,Gorelick NJ

    更新日期:1996-01-01 00:00:00

  • Application of the TGx-28.65 transcriptomic biomarker to classify genotoxic and non-genotoxic chemicals in human TK6 cells in the presence of rat liver S9.

    abstract::In vitro transcriptional signatures that predict toxicities can facilitate chemical screening. We previously developed a transcriptomic biomarker (known as TGx-28.65) for classifying agents as genotoxic (DNA damaging) and non-genotoxic in human lymphoblastoid TK6 cells. Because TK6 cells do not express cytochrome P450...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.22004

    authors: Yauk CL,Buick JK,Williams A,Swartz CD,Recio L,Li HH,Fornace AJ Jr,Thomson EM,Aubrecht J

    更新日期:2016-05-01 00:00:00

  • Does increase in DNA repair allow "tolerance-to-insult" in chemical carcinogenesis? Skin tumor experiments with MGMT-overexpressing mice.

    abstract::Several genotoxicity endpoints have been evaluated to define nonlinear dose-responses for SN 1 and SN 2 alkylating genotoxicants. Dose-response studies acknowledging the process of multistage tumorigenesis are important; however, data pertaining nonlinearity are not yet available. In this communication, the role of DN...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.21834

    authors: Becker K,Thomas AD,Kaina B

    更新日期:2014-03-01 00:00:00

  • K-ras cancer gene mutations in lung tumors from female Swiss (CD-1) mice exposed transplacentally to 3'-azido-3'-deoxythymidine.

    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

    authors: Koujitani T,Ton TV,Lahousse SA,Hong HH,Wakamatsu N,Sills RC

    更新日期:2008-12-01 00:00:00

  • Mutagenicity of N- and O-acetyl derivatives of methyl 3,4-diphenyl-5-hydroxylamino-2-furoate and N-hydroxy-4-aminobiphenyl in Salmonella typhimurium.

    abstract::Methyl 3,4-diphenyl-5-hydroxylamino-2-furoate (N-OH-MDPF) (I), methyl 3,4-diphenyl-5-acetoxyamino-2-furoate (N-OAc-MDPF) (II), methyl 3,4-diphenyl-N-hydroxy-5-acetylamino-2-furoate (N-OH-MDPAF) (III), and methyl 3,4-diphenyl-N-acetoxy-5-acetylamino-2-furoate (N-OAc-MDPAF) (IV) were synthesized and tested for mutagenic...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.2850170204

    authors: Swaminathan S,Hatcher JF,Yamamoto K,Tanaka A,Ichikawa M,Bryan GT

    更新日期:1991-01-01 00:00:00

  • Monitoring humans for somatic mutation in the endogenous PIG-a gene using red blood cells.

    abstract::The endogenous X-linked PIG-A gene is involved in the synthesis of glycosyl phosphatidyl inositol (GPI) anchors that tether specific protein markers to the exterior of mammalian cell cytoplasmic membranes. Earlier studies in rodent models indicate that Pig-a mutant red blood cells (RBCs) can be induced in animals trea...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.20667

    authors: Dobrovolsky VN,Elespuru RK,Bigger CA,Robison TW,Heflich RH

    更新日期:2011-12-01 00:00:00

  • DNA damage in peripheral blood leukocytes of physically active individuals as measured by the alkaline single cell gel electrophoresis assay.

    abstract::DNA damage induced by physical activity and/or exercise has been reported under different conditions but not for individuals maintaining physical fitness by regular strenuous exercise. Therefore, we compared levels of DNA damage in blood leukocytes of 40 healthy individuals (35 males, 5 females) who regularly exercise...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.20457

    authors: Gandhi G,Chopra G

    更新日期:2009-05-01 00:00:00

  • Effects of iron oxide nanoparticles: cytotoxicity, genotoxicity, developmental toxicity, and neurotoxicity.

    abstract::Iron oxide nanoparticles (ION) with superparamagnetic properties hold great promise for use in various biomedical applications; specific examples include use as contrast agents for magnetic resonance imaging, in targeted drug delivery, and for induced hyperthermia cancer treatments. Increasing potential applications r...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章,评审

    doi:10.1002/em.21909

    authors: Valdiglesias V,Kiliç G,Costa C,Fernández-Bertólez N,Pásaro E,Teixeira JP,Laffon B

    更新日期:2015-03-01 00:00:00

  • Sister chromatid exchanges in chick embryos after treatment with the phenoxy herbicide MCPA.

    abstract::The phenoxyherbicide and peroxisome proliferator 2-methyl-4-chlorophenoxyacetic acid (MCPA) was tested for its ability to induce sister-chromatid exchanges (SCE) in chick embryos. Erbitox E30 (a commercial formulation containing 28% MCPA sodium potassium salt as active ingredient) was injected into the air chamber in ...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.2850190411

    authors: Arias E

    更新日期:1992-01-01 00:00:00

  • DNA sequence analysis of interlocus recombination between the human T-cell receptor gamma variable (GV) and beta diversity-joining (BD/BJ) sequences on chromosome 7 (inversion 7).

    abstract::V(D)J recombinase-mediated recombination between the T-cell receptor (TCR) gamma variable (GV) genes at chromosome 7p15 and the TCR beta joining (BJ) genes at 7q35 leads to the formation of a hybrid TCR gene. These TCR gamma/beta interlocus rearrangements occur at classic V(D)J recombination signal sequences (RSS) and...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.10099

    authors: Ballinger SW,Judice SA,Nicklas JA,Albertini RJ,O'Neill JP

    更新日期:2002-01-01 00:00:00

  • 5-Azacytidine-induced 6-thioguanine resistance at the gpt locus in AS52 cells: cellular response.

    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

    authors: Spencer DL,Caspary WJ,Hines KC,Tindall KR

    更新日期:1996-01-01 00:00:00

  • Confirmation of the chromosome damaging effects of lamivudine in in vitro human peripheral blood lymphocytes.

    abstract::The aim of this study was to investigate genotoxic effects of lamivudine (an analogue of cytidine) using in vitro sister chromatid exchange (SCE), chromosome aberration (CA), and micronucleus (MN) tests in human peripheral lymphocytes. The cells were treated with 75, 100, 125, and 150 microg/ml concentrations of lamiv...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.20393

    authors: Bayram S,Topaktaş M

    更新日期:2008-05-01 00:00:00

  • Cytocidal and filamentous response of Escherichia coli cells exposed to low concentrations of hydrogen peroxide and hydroxyl radical scavengers.

    abstract::The hydroxyl radical scavengers thiourea, ethanol, and dimethyl sulfoxide significantly reduced the killing of Escherichia coli elicited by low concentrations of H2O2 (resulting in mode 1 killing) when treatments with the oxidant and the scavengers were performed in a complete growth medium (K medium) but not in M9 sa...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.2850180105

    authors: Brandi G,Salvaggio L,Cattabeni F,Cantoni O

    更新日期:1991-01-01 00:00:00

  • Mutagenicity and antimutagenicity of hispidulin and hortensin, the flavonoids from Millingtonia hortensis L.

    abstract::Studies of the mutagenicity and antimutagenicity of hispidulin and hortensin, the flavonoids from Millingtonia hortensis L. (Bignoniaceae), were performed using the liquid preincubation method of the Salmonella/microsome test. At the highest dose tested, 100 micrograms/plate, both compounds showed no mutagenicity and ...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.2850200409

    authors: Chulasiri M,Bunyapraphatsara N,Moongkarndi P

    更新日期:1992-01-01 00:00:00

  • In vitro effects of 1-MHz ultrasound on the mitotic spindle.

    abstract::The effects of ultrasound on the cytoskeleton, comprising microtubules, had been studied decades ago. Nonetheless, very little attention has been paid to the effects of ultrasound on the mitotic spindle, which is also formed by microtubules. In this study, we treated human fibroblasts and human cancer cells (HeLa and ...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.22287

    authors: Udroiu I,Coluzzi E,Bedini A,Giliberti C,Palomba R,Sgura A

    更新日期:2019-08-01 00:00:00

  • Mutagenicity and DNA adduct formation by aristolochic acid in the spleen of Big Blue® rats.

    abstract::Aristolochic acid (AA) is a potent human nephrotoxin and carcinogen. We previously reported that AA treatment resulted in DNA damage and mutation in the kidney and liver of rats. In this study, we have determined the DNA adducts and mutations induced by AA in rat spleen. Big Blue® transgenic rats were gavaged with 0, ...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.21696

    authors: McDaniel LP,Elander ER,Guo X,Chen T,Arlt VM,Mei N

    更新日期:2012-06-01 00:00:00

  • Similar polycyclic aromatic hydrocarbon and genotoxicity profiles of atmospheric particulate matter from cities on three different continents.

    abstract::The extractable organic material (EOM) from atmospheric total suspended particles (TSP) contains several organic compounds including non-substituted polycyclic aromatic hydrocarbons (PAHs), alkyl-PAHs, and nitro-PAHs. These chemicals seem to be among the key drivers of TSP genotoxicity. We have shown previously that t...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.22377

    authors: Maselli BS,Cunha V,Lim H,Bergvall C,Westerholm R,Dreij K,Watanabe T,Cardoso AA,Pozza SA,Umbuzeiro GA,Kummrow F

    更新日期:2020-06-01 00:00:00

  • Gender difference in DNA adduct levels among nonsmoking lung cancer patients.

    abstract::Lung cancer is the leading cause of cancer mortality in Taiwanese women. Cigarette smoking cannot explain the high lung cancer mortality in this population because less than 10% of women in Taiwan are smokers. Therefore, environmental factors other than smoking may play an important role in lung cancer development in ...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.1037

    authors: Cheng YW,Hsieh LL,Lin PP,Chen CP,Chen CY,Lin TS,Su JM,Lee H

    更新日期:2001-01-01 00:00:00

  • Determination of genotoxic and other effects in mice following short term repeated-dose and subchronic inhalation exposure to phosphine.

    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

    authors: Barbosa A,Rosinova E,Dempsey J,Bonin AM

    更新日期:1994-01-01 00:00:00

  • Induced mutations in M13mp2 phage DNA exposed to N-nitrosopyrrolidine with UVA irradiation.

    abstract::It is known that N-nitrosopyrrolidine (NPYR), a carcinogen in rodents, is metabolically activated by microsomal cytochrome P450 to form an alpha-hydroxylated derivative, which induces mutations. The mutations have been demonstrated by use of Salmonella typhimurium and Escherichia coli. We discovered directly acting mu...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:

    authors: Arimoto-Kobayashi S,Inada N,Anma N,Shimada H,Hayatsu H

    更新日期:1999-01-01 00:00:00

  • Integrated approach to the in vivo genotoxic effects of a titanium dioxide nanomaterial using LacZ plasmid-based transgenic mice.

    abstract::Titanium dioxide (TiO2 ) nanomaterials (NMs) are widely used in a diversity of products including cosmetics, pharmaceuticals, food, and inks, despite uncertainties surrounding the potential health risks that they pose to humans and the environment. Previous studies on the genotoxicity of TiO2 have reported discrepant ...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.21864

    authors: Louro H,Tavares A,Vital N,Costa PM,Alverca E,Zwart E,de Jong WH,Fessard V,Lavinha J,Silva MJ

    更新日期:2014-07-01 00:00:00

  • Association of cytochrome P450 1B1 haplotypes with head and neck cancer risk.

    abstract::Genetic polymorphisms have been reported in several cytochrome P450 (CYP) genes, including CYP1B1 which metabolically activates procarcinogens present in tobacco to carcinogenic intermediates. This study used a case-control approach in North Indian population to determine associations between genetic variants in CYP1B...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.22098

    authors: Katiyar T,Maurya SS,Hasan F,Singh AP,Khan AJ,Hadi R,Singh S,Bhatt MLB,Parmar D

    更新日期:2017-07-01 00:00:00

  • Report and summary of the major conclusions from statistics in genotoxicity testing working group from the International Workshop on Genotoxicity Test Procedures (IWGTP), March 1999.

    abstract::A working group of five statisticians experienced in the use of statistical methods in mutagenicity reviewed aspects of the statistical analysis of genotoxicity test procedures. Issues discussed included methods for integrating biological importance and statistical significance, the relationship of the experimental un...

    journal_title:Environmental and molecular mutagenesis

    pub_type:

    doi:

    authors: Lovell DP,Yoshimura I,Hothorn LA,Margolin BH,Soper K

    更新日期:2000-01-01 00:00:00

  • Mitochondrial mutations and human disease.

    abstract::The mitochondrial genome is essential for producing ATP (adenosine 5'-triphosphate) via oxidative phosphorylation. The gradual decline of mitochondrial function with age has long been postulated as a factor in aging. More recently, a variety of diseases have been related to molecular defects in human mitochondrial DNA...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章,评审

    doi:10.1002/em.2850250607

    authors: Grossman LI

    更新日期:1995-01-01 00:00:00

  • Global regulatory requirements for mutagenicity assessment in the registration of industrial chemicals.

    abstract::Mutagenicity is an important toxicological endpoint that requires thorough evaluation during the industrial chemical registration process. Regulatory requirements for mutagenicity assessment in registration of industrial chemicals vary in geographic regions (and in some cases by intended application). Here we compile ...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章,评审

    doi:10.1002/em.22096

    authors: Ji Z,Ball NS,LeBaron MJ

    更新日期:2017-06-01 00:00:00

  • Types of chromosomal aberrations induced by seed aging in Crepis capillaris.

    abstract::The types of chromosomal aberrations during the aging of Crepis capillaris (Hawksbeard; fam. Asteraceae) seeds were investigated. Seeds were stored at 22 degrees C for 2, 4, 6, and 8 years. Chromosomal aberrations were analyzed in metaphase chromosomes at the first and second mitotic cycles. A colchicine block was use...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.2850230410

    authors: Dimitrov BD

    更新日期:1994-01-01 00:00:00