Extrapolation of in vitro structural alerts for mutagenicity to the in vivo endpoint.

Abstract:

:As part of the hazard and risk assessment of chemicals in man, it is important to assess the ability of a chemical to induce mutations in vivo. Because of the commonalities in the molecular initiating event, mutagenicity in vitro can correlate well to the in vivo endpoint for certain compound classes; however, the difficulty lies in identifying when this correlation holds true. In silico alerts for in vitro mutagenicity may therefore be used as the basis for alerts for mutagenicity in vivo where an expert assessment is carried out to establish the relevance of the correlation. Taking this into account, a data set of publicly available transgenic rodent gene mutation assay data, provided by the National Institute of Health Sciences of Japan, was processed in the expert system Derek Nexus against the in vitro mutagenicity endpoint. The resulting predictivity was expertly reviewed to assess the validity of the observed correlations in activity and mechanism of action between the two endpoints to identify suitable in vitro alerts for extension to the in vivo endpoint. In total, 20 alerts were extended to predict in vivo mutagenicity, which has significantly improved the coverage of this endpoint in Derek Nexus against the data set provided. Updating the Derek Nexus knowledge base in this way led to an increase in sensitivity for this data set against this endpoint from 9% to 66% while maintaining a good specificity of 89%.

journal_name

Mutagenesis

journal_title

Mutagenesis

authors

Tennant RE,Guesné SJ,Canipa S,Cayley A,Drewe WC,Honma M,Masumura K,Morita T,Stalford SA,Williams RV

doi

10.1093/mutage/gey030

subject

Has Abstract

pub_date

2019-03-06 00:00:00

pages

111-121

issue

1

eissn

0267-8357

issn

1464-3804

pii

5114299

journal_volume

34

pub_type

杂志文章
  • Temperature and time effects on mutagen production in cooked lamb meat.

    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

    authors: Sflomos C,Papadopoulou R,Athanasiou K

    更新日期:1989-05-01 00:00:00

  • Direct and indirect non-disjunction in the origin of trisomy in cultured human lymphocytes.

    abstract::The aim of the present work was to investigate the processes involved in the origin of trisomic karyotypes, i.e. co-migration of sister chromatids (mitotic non-disjunction, MND) and recovery of micronuclei (MN) originating from lagging chromosomes/chromatids at anaphase (mitotic indirect non-disjunction, MIND), and to...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/14.6.557

    authors: Minissi S,Degrassi F,Tanzarella C,Gustavino B

    更新日期:1999-11-01 00:00:00

  • An improved assay for radiation-induced chromatid breaks using a colcemid block and calyculin-induced PCC combination.

    abstract::We report on a new method for the study of radiation-induced chromatid breaks in stimulated human peripheral blood T lymphocytes, involving a combination of a 1-h colcemid block and a short (15 min) calyculin A treatment. We find that this procedure eliminates the problem of centromere splitting when calyculin A is us...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/gen009

    authors: Shovman O,Riches AC,Adamson D,Bryant PE

    更新日期:2008-07-01 00:00:00

  • Pms2 deficiency results in increased mutation in the Hprt gene but not the Tk gene of Tk(+/-) transgenic mice.

    abstract::The effects of deficiency in the DNA mismatch repair (MMR) protein Pms2 were investigated using the endogenous mouse Hprt and Tk genes as reporters of intragenic mutation and loss of heterozygosity (LOH). Pms2(-/-)Tk(+/-), Pms2(+/+)Tk(+/-), Pms2(+/-)Tk(+/-) and Pms2(-/-)Tk(-/-) mice were bred from Pms2(+/-)Tk(+/-) mic...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/geg007

    authors: Dobrovolsky VN,McKinzie PB,Shaddock JG,Mittelstaedt RA,Heflich RH,Parsons BL

    更新日期:2003-07-01 00:00:00

  • A proposal for a two-dose/single-sample in vivo/in vitro rat hepatocyte unscheduled DNA synthesis assay.

    abstract::We have developed a two dose/single-sample protocol for the in vivo/in vitro rat hepatocyte unscheduled DNA synthesis (UDS) assay. In order to enhance the effectiveness of grain detection by image analysis we found minor technical modifications to be beneficial. These included the use of 3% acetic acid in ethanol (or ...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/11.1.19

    authors: Amphlett NW,Mitchell ID,Rees RW,Haynes GA

    更新日期:1996-01-01 00:00:00

  • Cytogenetic biomonitoring in a Spanish group of agricultural workers exposed to pesticides.

    abstract::Sister chromatid exchanges (SCE) and chromosome aberrations (CA) were studied in the lymphocytes of 70 male agricultural workers occupationally exposed to several pesticides and 69 matched controls, without indication of exposure to pesticides, from 'El Maresme' (Barcelona, Spain), Comparison between both groups revea...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/8.6.511

    authors: Carbonell E,Xamena N,Creus A,Marcos R

    更新日期:1993-11-01 00:00:00

  • Differential chromosome behaviour in mammalian oocytes exposed to the tranquilizer diazepam in vitro.

    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

    authors: Sun F,Yin H,Eichenlaub-Ritter U

    更新日期:2001-09-01 00:00:00

  • Haemoglobin adducts as biomarkers of occupational exposure to 1,3-butadiene.

    abstract::Adducts of 1,2-epoxy-3-butene (EB) with haemoglobin were monitored in 17 workers from the 1,3-butadiene (BD) production unit of a petrochemical plant and in nine referents employed at the same factory but not exposed to BD. The air concentrations of BD were determined using stationary and personal monitoring. The ambi...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/11.2.145

    authors: Osterman-Golkar S,Peltonen K,Anttinen-Klemetti T,Landin HH,Zorcec V,Sorsa M

    更新日期:1996-03-01 00:00:00

  • Functional analysis of the new barley gene HvKu80 indicates that it plays a key role in double-strand DNA break repair and telomere length regulation.

    abstract::Genotoxic stress causes a reduced stability of the plant genome and has a detrimental effect on plant growth and productivity. Double-strand breaks (DSBs) are the most harmful of all DNA lesions because they cause the loss of genetic information on both strands of the DNA helix. In the presented study the coding and g...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/gev033

    authors: Stolarek M,Gruszka D,Braszewska-Zalewska A,Maluszynski M

    更新日期:2015-11-01 00:00:00

  • A test of the mutagenicity of cooked meats in vivo.

    abstract::There is a correlation between intestinal cancer and diets high in meat, so fried beef, chicken, lamb, pork and fish were tested for their ability to induce mutations in the small intestine of mice. The mice were bred to be heterozygous at the Dlb-1 locus so that loss of the dominant Dlb-1 b allele by mutation could b...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/16.2.103

    authors: Heddle JA,Knize MG,Dawod D,Zhang XB

    更新日期:2001-03-01 00:00:00

  • Wavelength dependent responses of primary human keratinocytes to combined treatment with benzo[a]pyrene and UV light.

    abstract::The major risk factor for skin cancer is exposure to UV radiation from sunlight, but other environmental exposures may also play a role in combination with UV. We have studied the effects of combined exposure of primary human skin cells in vitro to UVA, UVB or UVC with benzo[a] pyrene (BaP), an environmental carcinoge...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/gei042

    authors: Crallan RA,Ingham E,Routledge MN

    更新日期:2005-07-01 00:00:00

  • Increased translocation frequency of chromosomes 7, 11 and 14 in lymphocytes from patients with neurocysticercosis.

    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

    authors: Herrera LA,Rodríguez U,Gebhart E,Ostrosky-Wegman P

    更新日期:2001-11-01 00:00:00

  • Microwell mutation assays: evaluation of ethylmethanesulphonate, benzo[a]pyrene and benzidine using the tk locus in L5178Y mouse lymphoma cells.

    abstract::As part of the third UKEMS collaborative trial, ICI Central Toxicology Laboratory (CTL) tested the three study chemicals ethylmethanesulphonate (EMS), benzo[a]pyrene (B[a]P) and benzidine (BZD) in a microwell adaptation of the L5178Y gene mutation assay using the thymidine kinase (tk) locus. Cofactors for metabolic ac...

    journal_title:Mutagenesis

    pub_type: 临床试验,杂志文章,多中心研究

    doi:

    authors: Clay P,Cross MF

    更新日期:1990-01-01 00:00:00

  • Cytogenetic detection of a trans-species bystander effect: induction of sister chromatid exchanges in murine 3T3 cells by ganciclovir metabolized in HSV thymidine kinase gene-transfected Chinese hamster ovary cells.

    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

    authors: Thust R,Tomicic MT,Gräbner R,Friedrichs C,Wutzler P,Kaina B

    更新日期:2004-01-01 00:00:00

  • Use of the SOS chromotest, the Ames-fluctuation test and the newt micronucleus test to study the genotoxicity of four trihalomethanes.

    abstract::Three short-term assays (the SOS chromotest, the Ames-fluctuation test and the newt micronucleus test) were carried out to evaluate the genotoxicity of four trihalomethanes (chloroform, bromodichloromethane, chlorodibromomethane and bromoform). With the SOS chromotest, all the chemicals studied except chloroform were ...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/10.4.333

    authors: Le Curieux F,Gauthier L,Erb F,Marzin D

    更新日期:1995-07-01 00:00:00

  • A modified protocol for the cytochalasin B in vitro micronucleus assay using whole human blood or separated lymphocyte cultures.

    abstract::A modified protocol is described for the in vitro analysis of micronuclei in whole blood or separated lymphocyte cultures. The induction of binucleate cells by various concentrations of cytochalasin B (3, 4.5 or 6 micrograms/ml) was examined at two harvest times (68 or 72 h). An optimal yield was obtained by adding cy...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/8.4.317

    authors: Ellard S,Parry EM

    更新日期:1993-07-01 00:00:00

  • Dietary sugars and related endogenous advanced glycation end-products increase chromosomal DNA damage in WIL2-NS cells, measured using cytokinesis-block micronucleus cytome assay.

    abstract::This study investigated the effect of glucose and fructose, and advanced glycation end-products (AGEs) on genome damage in WIL2-NS cells, measured using the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The effect of AGEs was investigated using the bovine serum albumin (AGE-BSA) model system induced either w...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/geaa002

    authors: Deo P,McCullough CL,Almond T,Jaunay EL,Donnellan L,Dhillon VS,Fenech M

    更新日期:2020-03-27 00:00:00

  • DNA repair and the origins of urinary oxidized 2'-deoxyribonucleosides.

    abstract::Monitoring oxidative stress in vivo is made easier by the ability to use samples obtained non-invasively, such as urine. The analysis of DNA oxidation, by measurement of oxidized 2'-deoxyribonucleosides in urine, particularly 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), has been reported extensively in the literatur...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/geq031

    authors: Evans MD,Saparbaev M,Cooke MS

    更新日期:2010-09-01 00:00:00

  • A comparison of folic acid and 5-methyltetrahydrofolate for prevention of DNA damage and cell death in human lymphocytes in vitro.

    abstract::Folic acid (FA), the most oxidized and stable form of folate, is commonly used as a dietary supplement and in culture media. FA must be reduced and methylated to become the metabolically active form found in blood and utilized by tissues, i.e. 5-methyltetrahydrofolate (5-MeTHF). 5-MeTHF is the methyl group donor requi...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/18.1.81

    authors: Wang X,Fenech M

    更新日期:2003-01-01 00:00:00

  • Species differences in mutagenicity testing. II. Sister-chromatid exchange and micronucleus induction in rats, mice and Chinese hamsters treated with cyclophosphamide.

    abstract::Comparative investigations of sister-chromatid exchange (SCE) and micronucleus induction in the bone marrow of rats, mice and Chinese hamsters with the cytostatic alkylating mutagen cyclophosphamide (CP) revealed remarkable species differences in their mutagenic responses. With both test systems the sensitivities of t...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/1.6.419

    authors: Madle E,Korte A,Beek B

    更新日期:1986-11-01 00:00:00

  • Antioxidant, anticlastogenic and radioprotective effect of Coleus aromaticus on Chinese hamster fibroblast cells (V79) exposed to gamma radiation.

    abstract::Coleus aromaticus (Benth, Family: Laminaceae), Indian Oregano native to India and Mediterranean, is well known for its medicinal properties. A preliminary study was undertaken to elucidate in vitro free radical scavenging potential and inhibition of lipid peroxidation by C.aromaticus hydroalcoholic extract (CAE). Anti...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/gel023

    authors: Rao BS,Shanbhoge R,Upadhya D,Jagetia GC,Adiga SK,Kumar P,Guruprasad K,Gayathri P

    更新日期:2006-07-01 00:00:00

  • Extended-term cultures of human T-lymphocytes: a practical alternative to primary human lymphocytes for use in genotoxicity testing.

    abstract::A simplified method, using recombinant interleukin-2, foetal bovine serum and freeze-killed feeder cells, has been developed for the mass culture of T-lymphocytes derived from human peripheral blood. In this protocol, bulk cultures can be cryopreserved approximately 8 days after initiation, and subsequent mass culture...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/10.3.189

    authors: O'Donovan MR,Freemantle MR,Hull G,Bell DA,Arlett CF,Cole J

    更新日期:1995-05-01 00:00:00

  • Biological significance of DNA damage induced by hyperbaric oxygen.

    abstract::Hyperbaric oxygen (HBO) treatment as used therapeutically has been shown to induce DNA damage in the alkaline comet assay with leukocytes from test subjects. Using formamidopyrimidine-DNA glycosylase, a DNA repair enzyme which specifically nicks DNA at sites of 8-oxoguanines and formamidopyrimidines, we have detected ...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/13.1.85

    authors: Speit G,Dennog C,Lampl L

    更新日期:1998-01-01 00:00:00

  • Evaluating microRNA profiles reveals discriminative responses following genotoxic or non-genotoxic carcinogen exposure in primary mouse hepatocytes.

    abstract::Chemical carcinogenesis can be induced by genotoxic (GTX) or non-genotoxic (NGTX) carcinogens. GTX carcinogens have a well-described mode of action. However, the complex mechanisms by which NGTX carcinogens act are less clear and may result in conflicting results between species [e.g. Wy-14,643 (Wy)]. We hypothesise t...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/gev036

    authors: Rieswijk L,Brauers KJ,Coonen ML,van Breda SG,Jennen DG,Kleinjans JC

    更新日期:2015-11-01 00:00:00

  • Metabolic formation, synthesis and genotoxicity of the N-hydroxy derivative of the food mutagen 2-amino-1-methyl-6-phenylimidazo (4,5-b) pyridine (PhIP).

    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

    authors: Frandsen H,Rasmussen ES,Nielsen PA,Farmer P,Dragsted L,Larsen JC

    更新日期:1991-01-01 00:00:00

  • Detection of nitro-azabenzo[a]pyrene derivatives in the semivolatile phase originating from airborne particulate matter, diesel and gasoline vehicles.

    abstract::Mutagens in the semivolatile phase of airborne particulate matter, diesel and gasoline engine emissions were investigated using chemical and biological assays. The previously unknown mutagens, 1-(3-)nitro-6-azabenzo[a]pyrenes (1-N-6-ABP and 3-N-6-ABP) and 1-(3-)nitro-6-azabenzo[a]pyrene-N-oxides (1-N-6-ABPO and 3-N-6-...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/9.1.47

    authors: Sera N,Fukuhara K,Miyata N,Tokiwa H

    更新日期:1994-01-01 00:00:00

  • Industrial Genotoxicology Group (IGG): Aneuploidy, White House Hotel, London, UK, 16 May 1997.

    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

    authors:

    更新日期:1998-07-01 00:00:00

  • Baseline levels of chromosome instability in the human lymphoblastoid cell TK6.

    abstract::Induced genomic instability in the human B lymphoblastoid cell line TK6 manifests itself as increases in end-to-end chromosome fusions and non-reciprocal chromosome translocations. It is not associated with elevated frequencies of specific locus mutations or other cytogenetic alterations. Previous studies on a limited...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/geh060

    authors: Schwartz JL,Jordan R,Evans HH,Lenarczyk M,Liber HL

    更新日期:2004-11-01 00:00:00

  • Molecular analysis of mutants obtained by treatment with alkylating agents in a quadruplicated white-ivory strain of Drosophila melanogaster.

    abstract::The use of a white-ivory (wi) strain of Drosophila melanogaster carrying four copies of this allele, (wi)4, has proved to be useful in detecting somatic mutation in genotoxicity testing. Nevertheless, until now very little information exists about the nature of the genetic effects detected in such a strain. This work ...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/14.2.187

    authors: Suárez S,Cabré O,Velázquez A,Marcos R,Xamena N

    更新日期:1999-03-01 00:00:00

  • Absence of evidence for mutagenicity of alcoholic beverages: an analysis of hprt mutant frequencies in 153 normal humans.

    abstract::A substantial database on hprt mutant frequency in circulating T-cells derived from 153 normal humans was analysed to determine if any effect of alcohol consumption could be detected. Alcohol intake (as reported in a questionnaire completed at the time of the blood sample) ranged from 0 to 35+ units per week. Donors w...

    journal_title:Mutagenesis

    pub_type: 杂志文章

    doi:10.1093/mutage/10.5.449

    authors: Cole J,Green MH

    更新日期:1995-09-01 00:00:00