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HERO ID
2111998
Reference Type
Journal Article
Title
Mutagenesis and carcinogenesis in nucleotide excision repair-deficient XPA knock out mice
Author(s)
van Steeg, H; Mullenders, LH; Vijg, J
Year
2000
Is Peer Reviewed?
1
Journal
Mutation Research
ISSN:
0027-5107
EISSN:
1873-135X
Publisher
Elsevier
Location
AMSTERDAM
Volume
450
Issue
1-2
Page Numbers
167-180
Language
English
PMID
10838141
DOI
10.1016/S0027-5107(00)00023-3
Web of Science Id
WOS:000087549500012
URL
https://www.proquest.com/docview/71157290?accountid=171501&bdid=13857&_bd=hf8CJO5jAPAcmuzIP5BSxL1xPxY%3D
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Abstract
Mice with a defect in the xeroderma pigmentosum group A (XPA) gene have a complete deficiency in nucleotide excision repair (NER). As such, these mice mimic the human XP phenotype in that they have a >1000-fold higher risk of developing UV-induced skin cancer. Besides being UV-sensitive, XPA(-/-) mice also develop internal tumors when they are exposed to chemical carcinogens. To investigate the effect of a total NER deficiency on the induction of gene mutations and tumor development, we crossed XPA(-/-) mice with transgenic lacZ/pUR288 mutation-indicator mice. The mice were treated with various agents and chemicals like UV-B, benzo[a]pyrene and 2-aceto-amino-fluorene. Gene mutation induction in several tumor target- and non-target tissues was determined in both the bacterial lacZ reporter gene and in the endogenous Hprt gene. Furthermore, alterations in the p53- and ras genes were determined in UV-induced skin tumors of XPA(-/-) mice. In this work, we review these results and discuss the applicability and reliability of enhanced gene mutant frequencies as early indicators of tumorigenesis.
Keywords
xeroderma pigmentosum; DNA repair gene; mutagenicity; lacZ reporter gene; Hprt gene; ras gene; p53 gene; UV light
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