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 language | English (US) |
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Pages (from-to) | 167-180 |
Number of pages | 14 |
Journal | Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis |
Volume | 450 |
Issue number | 1-2 |
DOIs | |
State | Published - May 30 2000 |
Externally published | Yes |
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