ArticleProceedings of the National Academy of Sciences of the United States of America2004
Human tumor p53 mutations are selected for in mouse embryonic fibroblasts harboring a humanized p53 gene.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Aristolochic acid-containing Chinese herbal medicine and upper urinary tract urothelial carcinoma in Taiwan: a narrative review.World journal of urology · 2023Pooled it
- Molecular and cell phenotype programs in oral epithelial cells directed by co-exposure to arsenic and smokeless tobacco.bioRxiv : the preprint server for biology · 2024Article
- Latency period of aristolochic acid-induced upper urinary tract urothelial carcinoma.Frontiers in public health · 2023Article
- Article
- Mutational signatures: emerging concepts, caveats and clinical applications.Nature reviews. Cancer · 2021Review
- Mutagenicity of acrylamide and glycidamide in human TP53 knock-in (Hupki) mouse embryo fibroblasts.Archives of toxicology · 2020Article
- Mutational signatures: experimental design and analytical framework.Genome biology · 2020Review
- Characterising Mutational Spectra of Carcinogens in the Tumour Suppressor GeneMethods and protocols · 2019Article
- The impact of p53 on aristolochic acid I-induced nephrotoxicity and DNA damage in vivo and in vitro.Archives of toxicology · 2019Article
- Experimental and pan-cancer genome analyses reveal widespread contribution of acrylamide exposure to carcinogenesis in humans.Genome research · 2019Article
- Validating the concept of mutational signatures with isogenic cell models.Nature communications · 2018Article
- Modeling cancer driver events in vitro using barrier bypass-clonal expansion assays and massively parallel sequencing.Oncogene · 2017Article
- Nutlin-3a selects for cells harbouring TP53 mutations.International journal of cancer · 2017Article
- Base changes in tumour DNA have the power to reveal the causes and evolution of cancer.Oncogene · 2017Review
- Damage-inducible intragenic demethylation of the human TP53 tumor suppressor gene is associated with transcription from an alternative intronic promoter.Molecular carcinogenesis · 2016Article
- Balkan endemic nephropathy: an update on its aetiology.Archives of toxicology · 2016Review
- The genome as a record of environmental exposure.Mutagenesis · 2015Article
- TP53 mutations induced by BPDE in Xpa-WT and Xpa-Null human TP53 knock-in (Hupki) mouse embryo fibroblasts.Mutation research · 2015Article
- Comparison of the metabolic activation of environmental carcinogens in mouse embryonic stem cells and mouse embryonic fibroblasts.Toxicology in vitro : an international journal published in association with BIBRA · 2015Article
- How the environment shapes cancer genomes.Current opinion in oncology · 2015Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To date, there has been no way to examine induced human p53 gene mutations in cell cultures exposed to mutagenic factors, other than by restriction site analysis. Here, we used embryonic cells from our Hupki (human p53 knock-in) mouse strain to generate human p53 DNA-binding domain (DBD) mutations experimentally. Twenty cultures of untreated primary mouse Hupki fibroblasts and 20 short-wavelength UV light (UVC)-treated cultures (20J/m(2)) were passaged >20 times. Established Hupki embryonic fibroblast cell lines (HUFs) were genotyped by dideoxy DNA sequencing of p53 exons 4-9. Seven of the HUFs harbored point mutations in the humanized p53 DBD. Of the 9 mutations (6 single- and 1 triple-site mutation), 2 were at the most frequently mutated codons in human cancers (c.248 and c.273). The Affymetrix p53 GeneChip assay also readily identified the 6 single-base substitutions. All mutations in HUFs from UV-treated cultures were at dipyrimidine sites, including 3 nontranscribed strand C -->T transitions. The mutant HUFs were deficient in p53 transactivation function, and missense mutants had high levels of nuclear p53 protein. In a second experiment, primary Hupki cells were exposed to the carcinogen aristolochic acid I (AAI). Five of 10 cultures that became established within 2 months harbored p53 DBD mutations. All were transversions, including 4 A --> T substitutions on the nontranscribed strand, a hallmark of DNA mutation by AAI. We conclude that establishment of Hupki mouse fibroblasts in culture readily selects for p53 DBD mutations found in human tumors, providing a basis for generating experimental mutation patterns in human p53.
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