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2111998 
Journal Article 
Mutagenesis and carcinogenesis in nucleotide excision repair-deficient XPA knock out mice 
van Steeg, H; Mullenders, LH; Vijg, J 
2000 
Mutation Research
ISSN: 0027-5107
EISSN: 1873-135X 
Elsevier 
AMSTERDAM 
450 
1-2 
167-180 
English 
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. 
xeroderma pigmentosum; DNA repair gene; mutagenicity; lacZ reporter gene; Hprt gene; ras gene; p53 gene; UV light