Mutation analysis with random DNA identifiers (MARDI) catalogs Pig-a mutations in heterogeneous pools of CD48-deficient T cells derived from DMBA-treated rats.

Abstract:

:Identification of mutations induced by xenotoxins is a common task in the field of genetic toxicology. Mutations are often detected by clonally expanding potential mutant cells and genotyping each viable clone by Sanger sequencing. Such a "clone-by-clone" approach requires significant time and effort, and sometimes is even impossible to implement. Alternative techniques for efficient mutation identification would greatly benefit both basic and regulatory genetic toxicology research. Here, we report the development of Mutation Analysis with Random DNA Identifiers (MARDI), a novel high-fidelity Next Generation Sequencing (NGS) approach that circumvents clonal expansion and directly catalogs mutations in pools of mutant cells. MARDI uses oligonucleotides carrying Random DNA Identifiers (RDIs) to tag progenitor DNA molecules before PCR amplification, enabling clustering of descendant DNA molecules and eliminating NGS- and PCR-induced sequencing artifacts. When applied to the Pig-a cDNA analysis of heterogeneous pools of CD48-deficient T cells derived from DMBA-treated rats, MARDI detected nearly all Pig-a mutations that were previously identified by conventional clone-by-clone analysis and discovered many additional ones consistent with DMBA exposure: mostly A to T transversions, with the mutated A located on the non-transcribed DNA strand.

journal_name

Environ Mol Mutagen

authors

Revollo JR,Crabtree NM,Pearce MG,Pacheco-Martinez MM,Dobrovolsky VN

doi

10.1002/em.21992

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

114-24

issue

2

eissn

0893-6692

issn

1098-2280

journal_volume

57

pub_type

杂志文章
  • Novel DNA repair alkyltransferase from Caenorhabditis elegans.

    abstract::O6-alkylguanine DNA-alkyltransferase (AGT) is a widely distributed DNA repair protein that protects living organisms from endogenous and exogenous alkylation damage to DNA at the O6-position of guanine. The search of the C. elegans genome database for an AGT protein revealed the presence of a protein (cAGT-2) with som...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.1077

    authors: Kanugula S,Pegg AE

    更新日期:2001-01-01 00:00:00

  • Evidence for an Aneugenic Mechanism of Action for Micronucleus Induction by Black Cohosh Extract.

    abstract::Black cohosh extract (BCE) is a popular botanical dietary supplement marketed to relieve symptoms of various gynecological ailments. Studies conducted by the National Toxicology Program (NTP) showed that BCE induces micronucleated erythrocytes in female rats and mice. Subsequently, the NTP showed that a variety of BCE...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.22334

    authors: Bernacki DT,Bryce SM,Bemis JC,Dertinger SD,Witt KL,Smith-Roe SL

    更新日期:2019-12-01 00:00:00

  • Acrylamide exposure induces a delayed unscheduled DNA synthesis in germ cells of male mice that is correlated with the temporal pattern of adduct formation in testis DNA.

    abstract::A study of meiotic and postmeiotic germ-cell-stage sensitivity of male mice to induction of unscheduled DNA synthesis (UDS) by acrylamide showed that DNA repair could be detected in early spermatocytes (after the last scheduled DNA synthesis) through about mid-spermatid stages. No DNA repair could be detected in later...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.2850160302

    authors: Sega GA,Generoso EE,Brimer PA

    更新日期:1990-01-01 00:00:00

  • Epigenetic responses following maternal dietary exposure to physiologically relevant levels of bisphenol A.

    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

    authors: Anderson OS,Nahar MS,Faulk C,Jones TR,Liao C,Kannan K,Weinhouse C,Rozek LS,Dolinoy DC

    更新日期:2012-06-01 00:00:00

  • DNA repair and gene therapy: implications for translational uses.

    abstract::Gene therapy has been proposed to have implications in the treatment of cancer. By genetically manipulating the hematopoietic stem cell compartment with genes that confer resistance to chemotherapeutic agents, the dose escalation that is necessary to effectively treat the cancers could potentially be achieved. DNA rep...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章,评审

    doi:10.1002/(sici)1098-2280(2000)35:2<71::aid-em1>3.0.

    authors: Limp-Foster M,Kelley MR

    更新日期:2000-01-01 00:00:00

  • Frequency of Hprt mutant lymphocytes and micronucleated erythrocytes in p53-haplodeficient mice treated perinatally with AZT and AZT in combination with 3TC.

    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

    authors: Dobrovolsky VN,Shaddock JG,Mittelstaedt RA,Bishop ME,Lewis SM,Lee FW,Aidoo A,Leakey JE,Dunnick JK,Heflich RH

    更新日期:2007-04-01 00:00:00

  • Molecular analyses of in vivo hprt mutations in human T-lymphocytes: IV. Studies in newborns.

    abstract::In order to characterize in vivo gene mutations that occur during fetal development, molecular analyses were undertaken of mutant 6-thioguanine resistant T-lymphocytes isolated from placental cord blood samples of 13 normal male newborns. These mutant T-cells were studied to define hypoxanthine-guanine phosphoribosylt...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.2850140404

    authors: McGinniss MJ,Nicklas JA,Albertini RJ

    更新日期:1989-01-01 00:00:00

  • Genetic toxicology testing of the antimalarial drugs chloroquine and a new analog, AQ-13.

    abstract::AQ-13 ([N1-(7-chloro-quinolin-4yl)-3-(N3,N3-diethylamino)propylamine] dihydrochloride trihydrate) is an aminoquinoline antimalarial drug that is effective against chloroquine-resistant strains of Plasmodium falciparum. It is structurally similar to the widely used chloroquine diphosphate (CQ). We evaluated these drugs...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.1052

    authors: Riccio ES,Lee PS,Winegar RA,Krogstad DJ,De D,Mirsalis JC

    更新日期:2001-01-01 00:00:00

  • Antioxidant and antimutagenic effects of the crude foliar extract and the alkaloid brachycerine of Psychotria brachyceras.

    abstract::The monoterpene indole alkaloid brachycerine from Psychotria brachyceras has been shown to be induced by UV and to have in vitro antioxidant activity, indicating a possible protective role against the secondary effects of this radiation. In this work, we have studied the antioxidant properties of brachycerine and a cr...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.20349

    authors: do Nascimento NC,Fragoso V,Moura DJ,e Silva AC,Fett-Neto AG,Saffi J

    更新日期:2007-12-01 00:00:00

  • Recent developments in frameworks to consider human relevance of hypothesized modes of action for tumours in animals.

    abstract::This paper summarizes recent developments in the continuing evolution of Human Relevance Frameworks to systematically consider the weight of evidence of hypothesized modes of action in animals and their potential human relevance for both cancer and non-cancer effects. These frameworks have been developed in initiative...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章,评审

    doi:10.1002/em.20369

    authors: Meek ME

    更新日期:2008-03-01 00:00:00

  • Induction of micronuclei in human sperm-hamster egg hybrids at the two-cell stage after in vitro gamma-irradiation of human spermatozoa.

    abstract::The efficiency of the micronucleus test to assess radiation-induced chromosomal damage in human spermatozoa has been investigated. Micronuclei were scored in human sperm-hamster egg hybrids at the two-cell stage, after exposure of human spermatozoa to in vitro gamma-rays at doses of 0.00, 0.10, 0.25, 0.50, 1.00, 2.00,...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.2850260407

    authors: Tusell L,Alvarez R,Caballín MR,Genescà A,Miró R,Ribas M,Egozcue J

    更新日期:1995-01-01 00:00:00

  • Alterations of plasma antioxidants and mitochondrial DNA mutation in hair follicles of smokers.

    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

    authors: Liu CS,Chen HW,Lii CK,Tsai CS,Kuo CL,Wei YH

    更新日期:2002-01-01 00:00:00

  • Genotoxicity of occupational exposure to wood dust: Micronucleus frequency and nuclear changes in exfoliated buccal mucosa cells.

    abstract::Occupational exposure to wood dust is associated with the occurrence of nasal cancer. In this study, we investigated micronuclei and nuclear changes (NCs: binucleates, karyorrhexis, karyolysis, and the "broken egg" effect) in exfoliated buccal cells of 20 workers exposed to wood dust and 20 age- and sex-matched contro...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.20257

    authors: Celik A,Kanik A

    更新日期:2006-12-01 00:00:00

  • Micronucleus induction by metronidazole in rat vaginal mucosa.

    abstract::Metronidazole (MTZ) is used for the treatment of many infectious diseases, including vaginal infections. While data indicate that MTZ is mutagenic and induces micronuclei in rodents, there is no information on the genotoxicity of MTZ in epithelial vaginal cells or cervical cells. In the present study, we have instille...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.20214

    authors: Ornelas-Aguirre JM,Gómez-Meda BC,Zamora-Perez AL,Ramos-Ibarra ML,Batista-González CM,Zúñiga-González GM

    更新日期:2006-06-01 00:00:00

  • Tissue-specific and time-dependent clonal expansion of ENU-induced mutant cells in gpt delta mice.

    abstract::DNA mutations play a crucial role in the origins of cancer, and the clonal expansion of mutant cells is one of the fundamental steps in multistage carcinogenesis. In this study, we correlated tumor incidence in B6C3F1 mice during the period after exposure to N-ethyl-N-nitrosourea (ENU) with the persistence of ENU-indu...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.22132

    authors: Nakayama T,Sawai T,Masuda I,Kaneko S,Yamauchi K,Blyth BJ,Shimada Y,Tachibana A,Kakinuma S

    更新日期:2017-10-01 00:00:00

  • A functional SNP in the 3'-UTR of TAP2 gene interacts with microRNA hsa-miR-1270 to suppress the gene expression.

    abstract::The transporter associated with antigen processing 2 (TAP2) is involved in the development of multidrug resistance and the etiology of immunological diseases. In this study, we investigated whether the expression of TAP2 can be perturbed by single nucleotide polymorphisms (SNPs) located in 3'-untranslated region (3'-U...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.22159

    authors: Knox B,Wang Y,Rogers LJ,Xuan J,Yu D,Guan H,Chen J,Shi T,Ning B,Kadlubar SA

    更新日期:2018-03-01 00:00:00

  • Human mutagens: evidence from paternal exposure?

    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

    authors: Narod SA,Douglas GR,Nestmann ER,Blakey DH

    更新日期:1988-01-01 00:00:00

  • Genotoxicity of hydrochlorothiazide in cultured human lymphocytes. I. Evaluation of chromosome delay and chromosome breakage.

    abstract::Hypertension is often treated with diuretics, like hydrochlorothiazide (HCTZ). Previous results on the in vitro genotoxicity of HCTZ are equivocal. In the present study, we have evaluated the genotoxicity of HCTZ in cultured human lymphocytes using the Cytokinesis Blocked Micronucleus (CBMN) assay. In addition, micron...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.20180

    authors: Andrianopoulos C,Stephanou G,Demopoulos NA

    更新日期:2006-04-01 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

  • Genotoxic effects of high dose rate X-ray and low dose rate gamma radiation in ApcMin/+ mice.

    abstract::Risk estimates for radiation-induced cancer in humans are based on epidemiological data largely drawn from the Japanese atomic bomb survivor studies, which received an acute high dose rate (HDR) ionising radiation. Limited knowledge exists about the effects of chronic low dose rate (LDR) exposure, particularly with re...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.22121

    authors: Graupner A,Eide DM,Brede DA,Ellender M,Lindbo Hansen E,Oughton DH,Bouffler SD,Brunborg G,Olsen AK

    更新日期:2017-10-01 00:00:00

  • Mutagenicity of the human carcinogen treosulphan, and its hydrolysis product, dl-1,2:3,4-diepoxybutane in mammalian cells.

    abstract::The cytotoxicity and mutagenicity of the human carcinogen, treosulphan, and its hydrolysis product, dl-1,2:3,4-diepoxybutane (DEB), were studied in Chinese hamster ovary, AS52, cells. Treosulphan (0.1-1.0 mM) is toxic and mutagenic at the gpt locus. A strong pH dependence was noted. DEB is cytotoxic and mutagenic at a...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.2850210113

    authors: Zhu S,Zeiger E

    更新日期:1993-01-01 00:00:00

  • 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

  • Is chronic use of hydroxyurea safe for patients with sickle cell anemia? An account of genotoxicity and mutagenicity.

    abstract::Sickle cell anemia (SCA) is a hereditary hematological disease that is characterized by a point mutation in the beta globin S gene and has no specific treatment; hydroxyurea (HU) is the only therapeutic agent used in clinical practice. In the present study, we evaluated the deoxyribonucleic acid (DNA) damage index (DI...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 信件

    doi:10.1002/em.22260

    authors: Maia Filho PA,Pereira JF,Almeida Filho TP,Cavalcanti BC,Sousa JC,Lemes RPG

    更新日期:2019-04-01 00:00:00

  • Time sequence of events leading to chromosomal aberration formation.

    abstract::Investigations have been carried out which have measured the influence of the repair polymerases on the yield of different types of chromosomal aberrations. The studies were mainly concerned with the effect of inhibiting the polymerases on the yield of aberrations. The polymerases fill in single strand regions, and th...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章,评审

    doi:10.1002/em.2850220405

    authors: Moore RC,Bender MA

    更新日期:1993-01-01 00:00:00

  • Structure-activity investigation of the potentiating effect of cyano substitution on nitroaniline mutagenicity in the ames test.

    abstract::2,6-Dicyano-4-nitroaniline and 2-cyano-4-nitroaniline (CNNA; 2-amino-5-nitrobenzonitrile) are potent mutagens in the Ames test, even though unsubstituted nitroanilines (NAs) are no more than weak mutagens. These compounds are putative reduction products of many commercial azo dyes, including Disperse Blue 165, Dispers...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.22161

    authors: Josephy PD,Dhanoa J,Elzawy G,Heney K,Petrie L,Senis C

    更新日期:2018-03-01 00:00:00

  • Novel transgenic rat for in vivo genotoxicity assays using 6-thioguanine and Spi- selection.

    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

    authors: Hayashi H,Kondo H,Masumura K,Shindo Y,Nohmi T

    更新日期:2003-01-01 00:00:00

  • Genotoxic and reproductive effects of an industrially contaminated soil on the earthworm Eisenia fetida.

    abstract::Polluted soil sampled from a former coking plant in Lorraine (France) was studied for its genotoxicity and reproductive effects on the Eisenia fetida earthworm. Genotoxicity was investigated by means of the single-cell gel electrophoresis (comet) assay on the coelomocytes of earthworms after 4 and 10 days of exposure ...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.20436

    authors: Bonnard M,Eom IC,Morel JL,Vasseur P

    更新日期:2009-01-01 00:00:00

  • APRT: a versatile in vivo resident reporter of local mutation and loss of heterozygosity.

    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.

    authors: Stambrook PJ,Shao C,Stockelman M,Boivin G,Engle SJ,Tischfield JA

    更新日期:1996-01-01 00:00:00

  • Evaluation of genetic damage in open-cast coal mine workers using the buccal micronucleus cytome assay.

    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

    authors: Rohr P,da Silva J,da Silva FR,Sarmento M,Porto C,Debastiani R,Dos Santos CE,Dias JF,Kvitko K

    更新日期:2013-01-01 00:00:00

  • Micronucleated erythrocytes in peripheral blood from neonate rats fed by nursing mothers exposed to X-rays.

    abstract::Most women with breast cancer can become pregnant and give birth while undergoing radiation therapy and breastfeeding is generally not contraindicated. The induction of long-lived reactive species in proteins, such as casein by X-ray radiation and DNA damage to unexposed organisms, has been shown when ingesting irradi...

    journal_title:Environmental and molecular mutagenesis

    pub_type: 杂志文章

    doi:10.1002/em.22426

    authors: Solórzano-Meléndez A,Rodrigo-Alarcón R,Gómez-Meda BC,Zamora-Pérez AL,Ortiz-García RG,Bayardo-López LH,González-Virgen R,Gallegos-Arreola MP,Zúñiga-González GM

    更新日期:2021-01-26 00:00:00