| Telomere elongation observed in immortalized human fibroblasts by treatment with 60Co gamma rays or 4-nitroquinoline 1-oxide. | |
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MedLine Citation:
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PMID: 8557247 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Telomeres are the tandemly repeated (TTAGGG)n sequences that make up the structural and functional ends of all chromosomes in mammals. Many lines of evidence indicate that telomeres stabilize chromosomes, prevent aberrant recombination, and direct chromosome attachment to the nuclear membrane. Since DNA polymerase requires a labile primer to initiate unidirectional 5'-3' DNA synthesis, some bases at the 3' end of each template strand are not copied unless special mechanisms bypass this end-replication problem. To overcome this problem, most eukaryotic cells use telomerase, an enzyme that elongates telomeres. However, this enzyme has not been detected in normal human cells, and these cells lose telomeres with cell division. Cellular senescence might be the result of this loss. Thus, activation of telomerase seems to be critical for the immortalization of human cell lines. In addition, substantial evidence indicates that immortalization in itself is a rate-limiting step for the malignant transformation of human cells. We have treated normal human fibroblasts (AD387, KMS-6, and OUMS-24 lines) intermittently with either 60Co gamma rays or 4-nitroquinoline 1-oxide (4NQO) during serial subcultivations, and have obtained three immortalized cell lines, SUSM-1, KMST-6, and OUMS-24F. In KMS-6 and OUMS-24, the mean terminal restriction fragment length significantly decreased as the population-doubling level increased. The rate of telomere loss was 40 and 50 bp/population doubling in the KMS-6 and OUMS-24 cell lines, respectively. Once these normal cell lines were immortalized, their telomeres became elongated. Similar data were obtained for AD387 cells and their immortalized SUSM-1 cells. These results suggest that telomeres play a critical role in cellular senescence and in the immortalization processes of human cells. |
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Authors:
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S Sugihara; K Mihara; T Marunouchi; H Inoue; M Namba |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Human genetics Volume: 97 ISSN: 0340-6717 ISO Abbreviation: Hum. Genet. Publication Date: 1996 Jan |
Date Detail:
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Created Date: 1996-02-23 Completed Date: 1996-02-23 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7613873 Medline TA: Hum Genet Country: GERMANY |
Other Details:
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Languages: eng Pagination: 1-6 Citation Subset: IM |
Affiliation:
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Department of Orthopaedic Surgery, Okayama University Medical School, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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4-Nitroquinoline-1-oxide
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pharmacology* Base Sequence Cell Line, Transformed Clone Cells Cobalt Radioisotopes Fetus Fibroblasts Gamma Rays* Humans Liver Male Molecular Sequence Data Regression Analysis Repetitive Sequences, Nucleic Acid Telomere / drug effects, radiation effects, ultrastructure* |
| Chemical | |
Reg. No./Substance:
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0/Cobalt Radioisotopes; 56-57-5/4-Nitroquinoline-1-oxide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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