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dc.contributor.authorKucab, JE
dc.contributor.authorPhillips, DH
dc.contributor.authorArlt, VM
dc.date.accessioned2018-08-08T10:47:44Z
dc.date.issued2012-04
dc.identifier3
dc.identifier.citationENVIRONMENTAL AND MOLECULAR MUTAGENESIS, 2012, 53 pp. 207 - 217
dc.identifier.issn0893-6692
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2304
dc.identifier.doi10.1002/em.21679
dc.description.abstractApproximately 50% of human tumors have a mutation in TP53. The pattern and spectra of TP53 mutations often differ between cancer types, perhaps due to different etiological factors. The Hupki (human TP53 knock-in) mouse embryo fibroblast (HUF) immortalization assay is useful for studying mutagenesis in the human TP53 gene by environmental carcinogens. Prior to initiating an immortalization assay, carcinogen treatment conditions must be optimized, which can require a large number of cells. As primary HUF cultures senesce within 2 weeks, restricting their use, we investigated whether immortalized HUFs retaining wild-type TP53 can be surrogates for primary HUFs in initial treatment optimization. DNA damage by eight compounds found in diesel exhaust, benzo[a]pyrene, 3-nitrobenzanthrone, 1-nitropyrene, 1,3-dinitropyrene, 1,6-dinitropyrene, 1,8-dinitropyrene, 6-nitrochrysene, and 3-nitrofluorene, was assessed by 32P-postlabeling and the alkaline comet assay in primary HUFs and in an immortal HUF cell line J201. For most compounds, higher levels of DNA adducts accumulated in J201 cells than in primary HUFs. This difference was not reflected in the comet assay or by cell viability changes. Experiments in three additional immortal HUF cell lines (AAI49, U56, and E2-143) confirmed strong differences in DNA adduct levels compared with primary HUFs. However, these did not correlate with the protein expression of Nqo1 or Nat1/2, or with gene expression of Cyp1a1 or Cyp1b1. Our results show that using immortal HUFs as surrogates for primary HUFs in genotoxicity screening has limitations and that DNA adduct formation is the best measure of genotoxicity of the nitro-polycyclic aromatic hydrocarbons tested in HUFs. Environ. Mol. Mutagen. 2012. (c) 2011 Wiley Periodicals, Inc.
dc.format.extent207 - 217
dc.languageeng
dc.language.isoeng
dc.publisherWILEY-BLACKWELL
dc.titleMetabolic activation of diesel exhaust carcinogens in primary and immortalized human TP53 knock-in (Hupki) mouse embryo fibroblasts
dc.typeJournal Article
rioxxterms.versionofrecord10.1002/em.21679
rioxxterms.licenseref.startdate2012-04
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfENVIRONMENTAL AND MOLECULAR MUTAGENESIS
pubs.notesaffiliation: Kucab, JE (Reprint Author), Kings Coll London, Analyt & Environm Sci Div, Environm Carcinogenesis Grp, Franklin Wilkins Bldg,150 Stamford St, London SE1 9NH, England. Kucab, Jill E.; Phillips, David H.; Arlt, Volker M., Kings Coll London, Analyt & Environm Sci Div, Environm Carcinogenesis Grp, London SE1 9NH, England. Kucab, Jill E.; Phillips, David H.; Arlt, Volker M., Inst Canc Res, Sect Mol Carcinogenesis, Sutton SM2 5NG, Surrey, England. keywords: DNA adducts; nitro-polycyclic aromatic hydrocarbons; metabolism; TP53; immortalization; Hupki keywords-plus: HEPATIC CYTOCHROME-P450 REDUCTASE; AIR-POLLUTANT 3-NITROBENZANTHRONE; TUMOR P53 MUTATIONS; FORMS DNA-ADDUCTS; ARISTOLOCHIC ACID; ENVIRONMENTAL-POLLUTANT; WILD-TYPE; GENE; MICE; MUTAGENICITY research-areas: Environmental Sciences & Ecology; Genetics & Heredity; Toxicology web-of-science-categories: Environmental Sciences; Genetics & Heredity; Toxicology author-email: [email protected] researcherid-numbers: perumal, murugiah/D-1565-2012 orcid-numbers: Arlt, Volker Manfred/0000-0003-4314-9318 Phillips, David/0000-0001-8509-3485 funding-acknowledgement: Institute of Cancer Research; Cancer Research UK; Cancer Research UK [14329]; Medical Research Council [G0801056B] funding-text: Grant sponsor: Institute of Cancer Research (Jill Kucab’s Ph.D. Studentship) and Cancer Research UK. number-of-cited-references: 45 times-cited: 10 usage-count-last-180-days: 0 usage-count-since-2013: 3 journal-iso: Environ. Mol. Mutagen. doc-delivery-number: 901PT unique-id: ISI:000300980000006 da: 2018-08-08
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Human Biomonitoring & Carcinogen Activation
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Human Biomonitoring & Carcinogen Activation
pubs.volume53
pubs.embargo.termsNot known
icr.researchteamHuman Biomonitoring & Carcinogen Activationen_US
dc.contributor.icrauthorPhillips, David Hunteren
dc.contributor.icrauthorArlt, Volker Manfreden
dc.contributor.icrauthorKucab, Jillen


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