TP53 mutations induced by BPDE in Xpa-WT and Xpa-Null human TP53 knock-in (Hupki) mouse embryo fibroblasts

Highlights • We have generated Xpa-Null Hupki (Human TP53 knock-in) mouse embryo fibroblasts (HUFs).• Xpa-Null HUFs can be used to study the impact of nucleotide excision repair on TP53 mutagenesis.• Xpa-Null HUFs exhibit increased sensitivity to benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE).• BPDE-induced TP53 mutagenesis is enhanced on the transcribed strand in Xpa-Null HUFs.• Several TP53 codons mutated by BPDE in HUFs are mutational hotspots in smokers’ lung cancer.

• Publication year

  2015

• Venue

  Mutation research

• Publication date

  2015-03-01

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1016/j.mrfmmm.2015.01.013PMID 25847421PMCID 4547099
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Modelling mutational landscapes of human cancers in vitro

  2014cited by this paper
• Cytochrome b5 and epoxide hydrolase contribute to benzo[a]pyrene-DNA adduct formation catalyzed by cytochrome P450 1A1 under low NADPH:P450 oxidoreductase conditions.

  2014cited by this paper
• ³²P-postlabeling analysis of DNA adducts.

  2014cited by this paper
• Nucleotide excision repair in eukaryotes.

  2013cited by this paper
• Abstract 4118: Hypoxia affects the metabolic activation and detoxification of the environmental mutagen benzo(a)pyrene

  2012cited by this paper
• Exposure to benzo[a]pyrene of Hepatic Cytochrome P450 Reductase Null (HRN) and P450 Reductase Conditional Null (RCN) mice: Detection of benzo[a]pyrene diol epoxide-DNA adducts by immunohistochemistry and 32P-postlabelling.

  2012cited by this paper
• Benzo[a]pyrene-induced transcriptomic responses in primary hepatocytes and in vivo liver: Toxicokinetics is essential for in vivo–in vitro comparisons

  2012cited by this paper
• Tumor suppressor p53 (TP53) at the crossroads of the exposome and the cancer genome

  2012cited by this paper
• TP53 mutations in human cancers: origins, consequences, and clinical use.

  2010cited by this paper
• Wild-type and Hupki (Human p53 Knock-in) Murine Embryonic Fibroblasts

  2010cited by this paper
• Unveiling the methylation status of CpG dinucleotides in the substituted segment of the human p53 knock‐in (Hupki) mouse genome

  2010cited by this paper
• Linking environmental carcinogen exposure to TP53 mutations in human tumours using the human TP53 knock‐in (Hupki) mouse model

  2010cited by this paper
• Applications of the human p53 knock‐in (Hupki) mouse model for human carcinogen testing

  2010cited by this paper
• TP53 mutation signature supports involvement of aristolochic acid in the aetiology of endemic nephropathy‐associated tumours

  2009influential reference
• Transcriptional control of human p53-regulated genes

  2008cited by this paper
• Cell-type-specific consequences of nucleotide excision repair deficiencies: Embryonic stem cells versus fibroblasts.

  2008cited by this paper
• The carcinogenic air pollutant 3-nitrobenzanthrone induces GC to TA transversion mutations in human p53 sequences.

  2008cited by this paper
• Identification through microarray gene expression analysis of cellular responses to benzo(a)pyrene and its diol-epoxide that are dependent or independent of p53.

  2008cited by this paper
• Both replication bypass fidelity and repair efficiency influence the yield of mutations per target dose in intact mammalian cells induced by benzo[a]pyrene-diol-epoxide and dibenzo[a,l]pyrene-diol-epoxide.

  2008cited by this paper
• Exocyclic amino groups of flanking guanines govern sequence-dependent adduct conformations and local structural distortions for minor groove-aligned benzo[a]pyrenyl-guanine lesions in a GG mutation hotspot context

  2007cited by this paper
• Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database

  2007cited by this paper
• Metabolic activation of benzo[a]pyrene in vitro by hepatic cytochrome P450 contrasts with detoxification in vivo: experiments with hepatic cytochrome P450 reductase null mice.

  2007cited by this paper
• Mutagenesis of human p53 tumor suppressor gene sequences in embryonic fibroblasts of genetically-engineered mice.

  2007cited by this paper
• Common tumour p53 mutations in immortalized cells from Hupki mice heterozygous at codon 72.

  2007influential reference
• Further studies with a cell immortalization assay to investigate the mutation signature of aristolochic acid in human p53 sequences.

  2006cited by this paper
• The Involvement of Ataxia-telangiectasia Mutated Protein Activation in Nucleotide Excision Repair-facilitated Cell Survival with Cisplatin Treatment*

  2006cited by this paper
• Differential removal of DNA adducts derived from anti-diol epoxides of dibenzo[a,l]pyrene and benzo[a]pyrene in human cells.

  2005cited by this paper
• Mechanisms of repair of polycyclic aromatic hydrocarbon-induced DNA damage

  2005cited by this paper
• Murine Fibroblasts Correlate with p 53 Mutations in Human Lung Tumors

  2005cited by this paper
• 32P-postlabeling analysis of DNA adducts.

  2005cited by this paper
• Oxygen in the Cultivation of Stem Cells

  2005cited by this paper
• p53 mutations in benzo(a)pyrene-exposed human p53 knock-in murine fibroblasts correlate with p53 mutations in human lung tumors.

  2005cited by this paper
• Human tumor p53 mutations are selected for in mouse embryonic fibroblasts harboring a humanized p53 gene.

  2004influential reference
• Transcription — guarding the genome by sensing DNA damage

  2004cited by this paper
• Mouse and human cells versus oxygen.

  2003cited by this paper
• Understanding the function–structure and function–mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis

  2003cited by this paper
• On the origin of G --> T transversions in lung cancer.

  2003cited by this paper
• Combined oral benzo[a]pyrene and inhalatory ozone exposure have no effect on lung tumor development in DNA repair-deficient Xpa mice.

  2003cited by this paper
• Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts

  2003cited by this paper
• Polκ protects mammalian cells against the lethal and mutagenic effects of benzo[a]pyrene

  2002cited by this paper
• Live or let die: the cell's response to p53

  2002cited by this paper
• Early p53-positive foci as indicators of tumor risk in ultraviolet-exposed hairless mice: kinetics of induction, effects of DNA repair deficiency, and p53 heterozygosity.

  2001cited by this paper
• Knock-in mice with a chimeric human/murine p53 gene develop normally and show wild-type p53 responses to DNA damaging agents: a new biomedical research tool

  2001cited by this paper
• Lung tumor KRAS and TP53 mutations in nonsmokers reflect exposure to PAH-rich coal combustion emissions.

  2001cited by this paper
• How nucleotide excision repair protects against cancer

  2001cited by this paper
• DNA Repair—Deficient Xpa and Xpa/p53+/- Knock-Out Mice: Nature of the Models

  2001cited by this paper
• Intestinal toxicity and carcinogenic potential of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in DNA repair deficient XPA-/- mice.

  2001cited by this paper
• Molecular analysis of p53 and K-ras in lung carcinomas of coal miners.

  2001cited by this paper
• UV-induced skin carcinogenesis in xeroderma pigmentosum group A (XPA) gene-knockout mice with nucleotide excision repair-deficiency.

  2001cited by this paper
• p53-dependent global genomic repair of benzo[a]pyrene-7,8-diol-9,10-epoxide adducts in human cells.

  2000cited by this paper
• Delay of DNA-adduct repair and severe toxicity in xeroderma pigmentosum group A gene (XPA) deficient mice treated with 2-amino-1-methyl-6-phenyl-imidazo [4,5-b] pyridine (PhIP).

  2000cited by this paper
• p53 and human cancer: the first ten thousand mutations.

  2000cited by this paper
• p53 mutational spectra and the role of methylated CpG sequences.

  2000cited by this paper
• Characterization of the mutational profile of (+)-7R,8S-dihydroxy-9S, 10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene at the hypoxanthine (guanine) phosphoribosyltransferase gene in repair-deficient Chinese hamster V-H1 cells.

  1999cited by this paper
• Defective global genome repair in XPC mice is associated with skin cancer susceptibility but not with sensitivity to UVB induced erythema and edema.

  1998cited by this paper
• Slow repair of bulky DNA adducts along the nontranscribed strand of the human p53 gene may explain the strand bias of transversion mutations in cancers

  1998cited by this paper
• Relative susceptibilities of XPA knockout mice and their heterozygous and wild-type littermates to UVB-induced skin cancer.

  1997cited by this paper
• Cytosine methylation determines hot spots of DNA damage in the human P53 gene.

  1997cited by this paper
• Induction of DNA adducts and mutations in spleen, liver and lung of XPA-deficient/lacZ transgenic mice after oral treatment with benzo[a]pyrene: correlation with tumour development.

  1997influential reference
• Blockage of RNA polymerase as a possible trigger for u.v. light-induced apoptosis.

  1996cited by this paper
• Preferential Formation of Benzo[a]pyrene Adducts at Lung Cancer Mutational Hotspots in P53

  1996cited by this paper
• DNA repair in human cells: quantitative assessment of bulky anti-BPDE-DNA adducts by non-competitive immunoassays.

  1995cited by this paper
• Selective recognition of the m5CpG dinucleotide sequence in DNA by mitomycin C for alkylation and cross-linking.

  1995cited by this paper
• Increased susceptibility to ultraviolet-B and carcinogens of mice lacking the DNA excision repair gene XPA

  1995influential reference
• Development of an in vitro primary screen for skin depigmentation and antimelanoma agents.

  1994cited by this paper
• Preferential repair of ultraviolet light‐induced dna damage in the transcribed strand of the human p53 gene

  1994cited by this paper
• Computer program for the analysis of mutational spectra: application to p53 mutations.

  1994cited by this paper
• Mutational specificity of the (+)-anti-diol epoxide of benzo[a]pyrene in a supF gene of an Escherichia coli plasmid: DNA sequence context influences hotspots, mutagenic specificity and the extent of SOS enhancement of mutagenesis.

  1993cited by this paper
• Benzo[a]pyrene-induced murine skin tumors exhibit frequent and characteristic G to T mutations in the p53 gene.

  1993cited by this paper
• Cancer. p53, guardian of the genome.

  1992influential reference
• p53, guardian of the genome

  1992cited by this paper
• p53 mutations in human cancers.

  1991cited by this paper
• Lack of a cell cycle-dependent strand bias for mutations induced in the HPRT gene by (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene in excision repair-deficient human cells.

  1991cited by this paper
• Lack of a Cell Cycle-dependent Strand Bias for Mutations Induced in the HPRT Gene by (±)-7β,8α-Dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene in Excision Repair-deficient Human Cells

  1991cited by this paper
• Base-sequence dependence of noncovalent complex formation and reactivity of benzo[a]pyrene diol epoxide with polynucleotides.

  1988cited by this paper
• Statistical test for the comparison of samples from mutational spectra.

  1987cited by this paper
• Statistical test for the comparison of samples from mutational spectra

  1987cited by this paper
• Base stacking and molecular polarizability: effect of a methyl group in the 5-position of pyrimidines.

  1987cited by this paper
• Hypersensitivity to cell killing and mutation induction by chemical carcinogens in an excision repair-deficient mutant of CHO cells.

  1983cited by this paper
• Carcinogenic epoxides of benzo[a]pyrene and cyclopenta[cd]pyrene induce base substitutions via specific transversions.

  1982cited by this paper
• SYNTHESIS AND REACTIONS OF DIOL EPOXIDES AND RELATED METABOLITES OF CARCINOGENIC HYDROCARBONS

  1980cited by this paper
• 6 – Synthesis and Reactions of Diol Epoxides and Related Metabolites of Carcinogenic Hydrocarbons

  1978cited by this paper
• Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test.

  1975cited by this paper
• Cáncer

  1939cited by this paper

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  2023cites this paper
• The landscape of genetic alterations of UVB‐induced skin tumors in DNA repair‐deficient mice

  2022cites this paper
• The Circ_CARM1 controls cell migration by regulating CTNNBIP1 in anti-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide-transformed 16HBE cells.

  2021cites this paper
• Mutagenicity of N‐hydroxy‐4‐aminobiphenyl in human TP53 knock‐in (Hupki) mouse embryo fibroblasts

  2021influential citation
• The role of DNA polymerase ζ in benzo[a]pyrene-induced mutagenesis in the mouse lung.

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• Mutagenicity of acrylamide and glycidamide in human TP53 knock-in (Hupki) mouse embryo fibroblasts

  2020cites this paper
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  2020cites this paper
• Mutational signatures: experimental design and analytical framework

  2020cites this paper
• The Impact of p53 on Aristolochic Acid I-Induced Gene Expression In Vivo

  2019cites this paper
• A Compendium of Mutational Signatures of Environmental Agents

  2019cites this paper
• The impact of p53 on aristolochic acid I-induced nephrotoxicity and DNA damage in vivo and in vitro

  2019cites this paper
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  2019cites this paper
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  2019influential citation
• Lung-Enriched Mutations in the p53 Tumor Suppressor: A Paradigm for Tissue-Specific Gain of Oncogenic Function

  2018influential citation
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  2018cites this paper
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