ArticleProceedings of the National Academy of Sciences of the United States of America2006
Carcinogens induce genome-wide loss of heterozygosity in normal stem cells without persistent chromosomal instability.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
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- World Trade Center dust exposure promotes cancer in PTEN-deficient mouse prostates.Cancer research communications · 2022Article
- Targeting loss of heterozygosity for cancer-specific immunotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Transcriptional activation of p21Oncotarget · 2018Article
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- The Damaging Effect of Passenger Mutations on Cancer Progression.Cancer research · 2017Article
- The Role of Chromosomal Instability and Epigenetics in Colorectal Cancers Lacking β-Catenin/TCF Regulated Transcription.Gastroenterology research and practice · 2016Article
- Phosphorylated RPA recruits PALB2 to stalled DNA replication forks to facilitate fork recovery.The Journal of cell biology · 2014Article
- Maintenance of genomic stability in mouse embryonic stem cells: relevance in aging and disease.International journal of molecular sciences · 2013Article
- Depletion of the bloom syndrome helicase stimulates homology-dependent repair at double-strand breaks in human chromosomes.DNA repair · 2011Article
- Genetic and epigenetic X-chromosome variations in a parthenogenetic human embryonic stem cell line.Journal of assisted reproduction and genetics · 2011Article
- Important role of indels in somatic mutations of human cancer genes.BMC medical genetics · 2010Article
- High-resolution DNA analysis of human embryonic stem cell lines reveals culture-induced copy number changes and loss of heterozygosity.Nature biotechnology · 2010Article
- Diepoxybutane activates the mitochondrial apoptotic pathway and mediates apoptosis in human lymphoblasts through oxidative stress.Toxicology in vitro : an international journal published in association with BIBRA · 2007Article
- Expression and loss of alleles in cultured mouse embryonic fibroblasts and stem cells carrying allelic fluorescent protein genes.BMC molecular biology · 2006Article
- Mutagenesis of diploid mammalian genes by gene entrapment.Nucleic acids research · 2006Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Widespread losses of heterozygosity (LOH) in human cancer have been thought to result from chromosomal instability caused by mutations affecting DNA repair/genome maintenance. However, the origin of LOH in most tumors is unknown. The present study examined the ability of carcinogenic agents to induce LOH at 53 sites throughout the genome of normal diploid mouse ES cells. Brief exposures to nontoxic levels of methylnitrosourea, diepoxybutane, mitomycin C, hydroxyurea, doxorubicin, and UV light stimulated LOH at all loci at frequencies ranging from 1-8 x 10(-3) per cell (10-123 times higher than in untreated cells). This greatly exceeds the frequencies at which these agents have been reported to induce point mutations and is comparable to the rates of LOH observed in ES cells lacking the gene responsible for Bloom syndrome, an inherited DNA repair defect that results in greatly increased risk of cancer. These results suggest that LOH contributes significantly to the carcinogenicity of a variety of mutagens and raises the possibility that genome-wide LOH observed in some human cancers may reflect prior exposure to genotoxic agents rather than a state of chromosomal instability during the carcinogenic process. Finally, as a practical matter, chemically induced LOH is expected to enhance the recovery of homozygous recessive mutants from phenotype-based genetic screens in mammalian cells.
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