| Breaks in DNA accompany estrogen-receptor-mediated cytotoxicity from 16 alpha[125I]iodo-17 beta-estradiol. | |
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MedLine Citation:
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PMID: 8423195 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Strategies for diagnosis and therapy in which sex steroid receptor ligands serve as carriers for radionuclides are attractive because a high incidence of carcinomas of the female genital tract and the breast that are seen clinically have an abundant expression of one or more of the receptor proteins. A radiohalogenated estrogen receptor (ER) ligand, 16 alpha-[123I]iodo-17 beta-estradiol [123I]E, has met clinical criteria for receptor-mediated diagnostic imaging. Its [125]I-labeled sister nuclide derivative [125I]E decays by orbital electron capture with emission of very-low-energy (Auger) electrons, which gives this latter radiohalogen the potential to serve in pharmaceuticals for radiotherapy; as examples, [125I]deoxyuridine, when incorporated into the DNA molecule, or [125I]E, when bound to the receptor within ER-rich tumor cells, are both cytotoxic in vitro. Whereas the mechanisms and subcellular changes that accompany the cytotoxicity from [125I]deoxyuridine are well documented in the form of aberrations and breaks in the cellular DNA, the effects at the subcellular level causing the cytotoxicity of the sex steroid receptor ligand [125I]E have not been characterized and are the focus of our study. We found that in a standard colony-forming assay the addition of [125I]E to the cultures decreased the survival rate of ER-positive MCF-7 cells in a dose-dependent manner. The decreased survival rate was prevented by the addition of competing excess radioinert ER ligand (diethylstilbestrol); [125I]E did not reduce survival in ER-negative MCF-7 cells. The [125I]E-induced and ER-mediated cytotoxicity was accompanied by aberrations in the DNA components of the nuclei of the cells. These included chromatid and chromosome breaks, gaps, and tri-radial chromosome formation. Our findings add plausibility and credence to the notion that the cytotoxicity imparted by Auger-electron-emitting radioligands for sex steroid receptors is in part attributable to radiodecay that causes double-stranded breakage of DNA. |
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Authors:
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M W Beckmann; A Scharl; B J Rosinsky; J A Holt |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of cancer research and clinical oncology Volume: 119 ISSN: 0171-5216 ISO Abbreviation: J. Cancer Res. Clin. Oncol. Publication Date: 1993 |
Date Detail:
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Created Date: 1993-02-24 Completed Date: 1993-02-24 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 7902060 Medline TA: J Cancer Res Clin Oncol Country: GERMANY |
Other Details:
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Languages: eng Pagination: 207-14 Citation Subset: IM |
Affiliation:
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Department of Obstetrics and Gynecology, Chicago Lying-in Hospital, University of Chicago, IL 60637-1470. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Chromosomes
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radiation effects Colony-Forming Units Assay DNA Damage / radiation effects* Estradiol / analogs & derivatives*, pharmacology Humans Iodine Radioisotopes* Radioligand Assay Receptors, Estrogen / radiation effects* Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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CA-27476/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Iodine Radioisotopes; 0/Receptors, Estrogen; 50-28-2/Estradiol; 71765-94-1/16 alpha-iodoestradiol |
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