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The influence of SV40 immortalization of human fibroblasts on p53-dependent radiation responsesThe simian virus 40 large tumor antigen (SV40 Tag) has been ascribed many functions critical to viral propagation, including binding to the mammalian tumor suppressor p53. Recent studies have demonstrated that SV40-transformed murine cells have functional p53. The status of p53 in SV40-immortalized human cells, however, has not been characterized. We have found that in response to ionizing radiation, p53-dependent p21 transactivation activity is present, albeit reduced, in SV40-immortalized cells and that this activity can be further reduced with either dominant negative p53 expression or higher SV40 Tag expression. Furthermore, overexpression of p53 in SV40-immortalized ataxia-telangiectasia (A-T) cells restores p53-dependent p21 induction to typical A-T levels. All SV40-immortalized cell lines exhibited an absence of G1 arrest. Moreover, all SV40-immortalized cell lines exhibited increased apoptosis relative to primary cells in response to ionizing radiation, suggesting that SV40 immortalization results in a unique phenotype with regard to DNA damage responses. Copyright 1999 Academic Press.
Document ID
20040142027
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Kohli, M.
(Georgetown University Medical Center 3970 Reservoir Road, N.W., Washington, DC 20007-2197, United States)
Jorgensen, T. J.
Date Acquired
August 22, 2013
Publication Date
April 2, 1999
Publication Information
Publication: Biochemical and biophysical research communications
Volume: 257
Issue: 1
ISSN: 0006-291X
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: P01-CA74175
CONTRACT_GRANT: 2P30-CA-51008
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Radiation Health
Non-NASA Center

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