| Spontaneous p53 mutation in murine mesothelial cells: increased sensitivity to DNA damage induced by asbestos and ionizing radiation. | |
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MedLine Citation:
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PMID: 8917699 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The p53 gene regulates the G1 cell cycle checkpoint in response to DNA damage. A primary murine mesothelial cell line (D9) spontaneously acquired a point mutation at codon 135 in exon 5 of the p53 gene, resulting in substitution of alanine for proline; early passage D9 cells expressed wild-type p53. The growth rate of late passage D9 cells that acquired the p53 mutation was increased compared to that of early passage cells; however, this mutation was not sufficient to confer tumorigenicity to this cell line. Mammalian cells that express wild-type p53 show a transient arrest in G1 after exposure to ionizing radiation. Early passage D9 cells showed a G1 arrest following ionizing radiation, while late passage D9 cells arrested in G2 or mitosis. The clastogenic effects of ionizing radiation can be demonstrated by the cytokinesis-arrested micronucleus assay. Following treatment with cytochalasin B to arrest cytokinesis, ionizing radiation induced micronuclei in 50% of late passage D9 cells compared to 15% of early passage cells. After exposure to 15 micrograms/cm2 of crocidolite asbestos fibers, 18% of late passage cells had micronuclei compared to 4% of early passage cells. It is hypothesized that loss of the G1 cell cycle checkpoint contributes to genetic instability in murine mesothelial cells. |
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Authors:
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C A Cistulli; T Sorger; J M Marsella; C A Vaslet; A B Kane |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Toxicology and applied pharmacology Volume: 141 ISSN: 0041-008X ISO Abbreviation: Toxicol. Appl. Pharmacol. Publication Date: 1996 Nov |
Date Detail:
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Created Date: 1996-12-23 Completed Date: 1996-12-23 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0416575 Medline TA: Toxicol Appl Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 264-71 Citation Subset: IM |
Affiliation:
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Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island 02912, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Asbestos / toxicity* Carcinogens / toxicity* Cell Cycle / radiation effects Cell Line DNA Damage / genetics* Epithelium / drug effects, radiation effects Genes, p53 / drug effects*, radiation effects* Mice Micronucleus Tests Mutagenicity Tests Point Mutation* Radiation, Ionizing* Sequence Analysis, DNA |
| Grant Support | |
ID/Acronym/Agency:
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R01 ES03721/ES/NIEHS NIH HHS; R01 ES05712/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Carcinogens; 1332-21-4/Asbestos |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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