title: The combined effects of xeroderma pigmentosum C deficiency and mutagens on mutation rates in the mouse germ line.
abstract: Spontaneous and induced mutation rates at two expanded simple tandem repeat (ESTR) loci were studied in the germ line of xeroderma pigmentosum group C (Xpc) knockout mice defective in global genome nucleotide excision repair. Spontaneous and radiation-induced mutation rates in homozygous Xpc(-/-) males were significantly higher than those in isogenic wild-type (Xpc(+/+)) and heterozygous (Xpc(+/-)) mice. In contrast, exposure to the monofunctional alkylating agent ethylnitrosourea resulted in similar increases in ESTR mutation rates across all genotypes. ESTR mutation spectra in the germ line of Xpc(-/-), Xpc(+/-) and Xpc(+/+) did not differ. Considering these data and the results of other publications, we propose that the Xpc-deficient mice possess a mutator phenotype in their germ line and somatic tissues that may significantly enhance carcinogenesis across multiple tissues.
authors.affiliation: Commissariat à l'Energie Atomique, Laboratoire de Génétique de la Radiosensibilité, Institut de Radiobiologie Cellulaire et Moléculaire, Direction des Sciences du Vivant, Fontenay aux Roses, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Miccoli
authors.forename: Karen L-A
authors.initials: KL
authors.lastname: Burr
authors.forename: Peter
authors.initials: P
authors.lastname: Hickenbotham
authors.forename: Errol C
authors.initials: EC
authors.lastname: Friedberg
authors.forename: Jaime F
authors.initials: JF
authors.lastname: Angulo
authors.forename: Yuri E
authors.initials: YE
authors.lastname: Dubrova
mesh_terms: D000818:Animals; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics*; D005038:Ethylnitrosourea / Q000494:pharmacology*; D018095:Germ-Line Mutation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009153:Mutagens / Q000494:pharmacology*; D020080:Tandem Repeat Sequences
chemical_list: D004268:DNA-Binding Proteins; D009153:Mutagens; C501002:Xpc protein, mouse; D005038:Ethylnitrosourea