title: Nucleotide excision repair- and p53-deficient mouse models in cancer research.
abstract: Cancer is caused by the loss of controlled cell growth due to mutational (in)activation of critical genes known to be involved in cell cycle regulation. Three main mechanisms are known to be involved in the prevention of cells from becoming cancerous; DNA repair and cell cycle control, important to remove DNA damage before it will be fixed into mutations and apoptosis, resulting in the elimination of cells containing severe DNA damage. Several human syndromes are known to have (partially) deficiencies in these pathways, and are therefore highly cancer prone. Examples are xeroderma pigmentosum (XP) caused by an inborn defect in the nucleotide excision repair (NER) pathway and the Li-Fraumeni syndrome, which is the result of a germ line mutation in the p53 gene. XP patients develop skin cancer on sun exposed areas at a relatively early age, whereas Li-Fraumeni patients spontaneously develop a wide variety of early onset tumors, including sarcomas, leukemia's and mammary gland carcinomas. Several mouse models have been generated to mimic these human syndromes, providing us information about the role of these particular gene defects in the tumorigenesis process. In this review, spontaneous phenotypes of mice deficient for nucleotide excision repair and/or the p53 gene will be described, together with their responses upon exposure to either chemical carcinogens or radiation. Furthermore, possible applications of these and newly generated mouse models for cancer will be given.
authors.affiliation: Laboratory of Toxicology, Pathology and Genetics, National Institute of Public Health and the Environment, P.O. Box 1, 3720 BA Bilthoven, The Netherlands.
authors.forename: Esther M
authors.initials: EM
authors.lastname: Hoogervorst
authors.forename: Harry
authors.initials: H
authors.lastname: van Steeg
authors.forename: Annemieke
authors.initials: A
authors.lastname: de Vries
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair; D016158:Genes, p53 / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D023421:Models, Animal; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D012106:Research