Document Detail


Ultraviolet hypermutability of a shuttle vector propagated in xeroderma pigmentosum variant cells.
MedLine Citation:
PMID:  8228338     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Patients with the variant form of xeroderma pigmentosum (XP) have clinical XP including a high frequency of skin cancer but, in contrast to the other forms of XP, have normal post-ultraviolet (UV) DNA excision repair and nearly normal post-UV survival. However, like excision repair-deficient XP cells, the XP variant cells are UV hypermutable. We used a UV-treated plasmid shuttle vector, pZ189, to examine the DNA repair defect in lymphoblastoid cells from an XP variant patient, XPPHBE, and a normal control. Plasmid repair, mutagenesis, and replication occur within transfected cells in a process dependent on the cells' repair capacity. With the XP variant cells post-UV, plasmid survival was normal with but there was an abnormally increased post-UV plasmid mutation frequency. Sequence analysis of the mutated plasmids revealed an increased frequency of plasmids with single base substitution mutations with the XP variant cells. As in earlier studies with UV mutagenesis, there was a predominance of G:C-->A:T base substitution mutations with plasmids recovered from both cell lines. The frequency of G:C-->C:G transversions was significantly higher with plasmids recovered from the XP variant cells than from normal cells. The location of mutations in the marker gene was non-random with different mutagenic hotspots found in plasmids recovered from the XP variant cells and from the normal cells. This study suggests that plasmid UV hypermutability in the presence of normal UV survival may be related to the increased UV skin cancer susceptibility of XP variant patients.
Authors:
H L Waters; S Seetharam; M M Seidman; K H Kraemer
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  101     ISSN:  0022-202X     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  1993 Nov 
Date Detail:
Created Date:  1993-11-26     Completed Date:  1993-11-26     Revised Date:  2008-08-12    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  744-8     Citation Subset:  IM    
Affiliation:
Laboratory of Molecular Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892.
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MeSH Terms
Descriptor/Qualifier:
Adult
Base Sequence
Cell Line
DNA Repair
Female
Genetic Vectors
Humans
Male
Molecular Sequence Data
Mutation*
Plasmids
Ultraviolet Rays
Xeroderma Pigmentosum / genetics*
Grant Support
ID/Acronym/Agency:
Z01 BC004517-31/BC/NCI NIH HHS

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


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