title: Age-dependent spontaneous mutagenesis in Xpc mice defective in nucleotide excision repair.
abstract: DNA damages caused by cellular metabolites and environmental agents induce mutations, that may predispose to cancer. Nucleotide excision repair (NER) is a major cellular defence mechanism acting on a variety of DNA lesions. Here, we show that spontaneous mutant frequencies at the Hprt gene increased 30-fold in T-lymphocytes of 1 year old Xpc-/- mice, possessing only functional transcription-coupled repair (TCR). Hprt mutant frequencies in Xpa-/- and Csb-/- mice that both have a defect in this NER subpathway, remained low during ageing. In contrast to current models, the elevated mutation rate in Xpc-/- mice does not lead to an increased tumour incidence or premature ageing. Oncogene (2000) 19, 5034 - 5037
authors.affiliation: Department of Radiation Genetics and Chemical Mutagenesis-MGC, Leiden University Medical Center, 2333 AL Leiden, The Netherlands.
authors.forename: S W
authors.initials: SW
authors.lastname: Wijnhoven
authors.forename: H J
authors.initials: HJ
authors.lastname: Kool
authors.forename: L H
authors.initials: LH
authors.lastname: Mullenders
authors.forename: A A
authors.initials: AA
authors.lastname: van Zeeland
authors.forename: E C
authors.initials: EC
authors.lastname: Friedberg
authors.forename: G T
authors.initials: GT
authors.lastname: van der Horst
authors.forename: H
authors.initials: H
authors.lastname: van Steeg
authors.forename: H
authors.initials: H
authors.lastname: Vrieling
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016296:Mutagenesis; D009374:Neoplasms, Experimental / Q000235:genetics; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics; D014983:Xeroderma Pigmentosum / Q000235:genetics*
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase