Document Detail


Transfected mutant p53 gene increases X-ray-induced cell killing and mutation in human fibroblasts immortalized with 4-nitroquinoline 1-oxide but does not induce neoplastic transformation of the cells.
MedLine Citation:
PMID:  7705936     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We introduced the mutant p53 gene (codon 273Arg-His) into human fibroblasts (SUSM-I cells) previously immortalized with 4-nitroquinoline I-oxide (4NQO) and obtained 2 clonal cell lines (SUSM-i/p53-1 and SUSM-1/p53-6) expressing the mutant p53. Since the genetic background of SUSM-1/p53 is the same as that of SUSM-1 except for the presence of the mutant p53, we expected to obtain more information on the mechanisms of p53 functions without the influence of other genetic differences by comparing cellular characteristics of both cell lines. SUSM-1/p53 cells became about twice as sensitive to the cytotoxic effects of X-rays as their parent SUSM-1 cells. Mutation frequency was determined by the appearance of hypoxanthine guanine phosphoribosyl transferase deficient (6-thioguanine resistant) cells. As a result, the mutation frequency of SUSM-1/p53 cells was about 5 times that of SUSM-1 cells transfected with or without the vector plasmid alone. Furthermore, when the SUSM-1/p53 cells were exposed to X-rays, the mutation frequency increased to about twice that of the non-irradiated SUSM-1/p53 cells. However, SUSM-1/p53 cells showed neither anchorage-independent growth in soft agar nor tumorigenicity in nude mice. These results indicate that the mutant p53 gene itself, which generally works in a dominant-negative way on cellular carcinogenesis, is not sufficient for neoplastic transformation of immortalized human cells, and that additional genetic change(s) may be necessary for transformation.
Authors:
K Kawashima; K Mihara; H Usuki; N Shimizu; M Namba
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  61     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  1995 Mar 
Date Detail:
Created Date:  1995-05-09     Completed Date:  1995-05-09     Revised Date:  2007-07-24    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  76-9     Citation Subset:  IM    
Affiliation:
Department of Cell Biology, Okayama University Medical School, Japan.
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MeSH Terms
Descriptor/Qualifier:
4-Nitroquinoline-1-oxide / pharmacology*
Animals
Base Sequence
Cell Death / radiation effects
Cell Division / physiology
Cell Line, Transformed
Cell Transformation, Neoplastic / genetics*
Fibroblasts / drug effects,  physiology*,  radiation effects
Genes, p53 / genetics*
Humans
Hypoxanthine Phosphoribosyltransferase / genetics
Mice
Mice, Nude
Molecular Sequence Data
Mutation
Radiation Tolerance / genetics*
Transfection
Chemical
Reg. No./Substance:
56-57-5/4-Nitroquinoline-1-oxide; EC 2.4.2.8/Hypoxanthine Phosphoribosyltransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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