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| Chromosomal instability and its relationship to other end points of genomic instability |
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| Author(s): Limoli CL, Kaplan MI, Corcoran J, Meyers M, Boothman DA, Morgan WF |
| Source: CANCER RESEARCH Volume: 57 Issue: 24 Pages: 5557-5563 Published: DEC 15 1997 |
| Times Cited: 72 References: 53 |
| Abstract: Chromosomal destabilization is one end point of the more general phenomenon of genomic instability. We previously established that chromosomal instability can manifest in clones derived from single progenitor cells several generations after X-irradiation. To understand the potential relationship between chromosomal destabilization and the other end points of genomic instability, we generated a series of chromosomally stable and unstable clones by exposure to X-rays, All clones were derived from the human-hamster hybrid line GM10115, which contains a single copy of human chromosome 4 in a background of 20-24 hamster chromosomes, These clones were then subjected to a series of assays to determine whether chromosomal instability is associated with a general "mutator phenotype" and whether it modulates other end points of genomic instability, Thus, we analyzed clones for sister chromatid exchange, delayed reproductive cell death, delayed mutation, mismatch repair, and delayed gene amplification, Statistical analyses performed on each group of chromosomally stable and unstable clones indicated that, although individual clones within each group were significantly different from unirradiated clones for many of the end points, there was no significant correlation between chromosomal instability and sister chromatid exchange, delayed mutation, and mismatch repair, Delayed gene amplification was found to be marginally correlated to chromosomal instability (P < 0.1), and delayed reproductive cell death (the persistent reduction in plating efficiency after irradiation) was found to be significantly correlated (P < 0.05). These correlations may be explained by chromosomal destabilization, which can mediate gene amplification and can result in cellular lethality. These data implicate multiple molecular and genetic pathways leading to different manifestations of genomic instability in GM10115 cells surviving exposure to DNA-damaging agents. |
| Document Type: Article |
| Language: English |
| Reprint Address: Limoli, CL (reprint author), Univ Calif San Francisco, Dept Radiat Oncol, Box 0750, San Francisco, CA 94143 USA |
Addresses:
1. Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA
2. Univ Calif San Francisco, Grad Grp Biophys, San Francisco, CA 94143 USA
3. Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA
4. Univ Wisconsin, Sch Med, Dept Human Oncol, Madison, WI 53792 USA
5. Ctr Comprehens Canc, Madison, WI 53792 USA |
| Publisher: AMER ASSOC CANCER RESEARCH, PO BOX 11806, BIRMINGHAM, AL 35202 USA |
| Subject Category: Oncology |
| IDS Number: YL378 |
| ISSN: 0008-5472 |
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