Mutagenesis and carcinogenesis in nucleotide excision repair-deficient XPA knock out mice

Harry Van Steeg, Leon H.F. Mullenders, Jan Vijg

Research output: Contribution to journalArticle

40 Scopus citations

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. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)167-180
Number of pages14
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume450
Issue number1-2
DOIs
StatePublished - May 30 2000
Externally publishedYes

Keywords

  • DNA repair gene
  • Hprt gene
  • Mutagenicity
  • UV light
  • Xeroderma pigmentosum
  • lacZ reporter gene
  • p53 gene
  • ras gene

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

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