The combined effects of xeroderma pigmentosum C deficiency and mutagens on mutation rates in the mouse germ line.
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.
Miccoli
Laurent
L
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.
Burr
Karen L-A
KL
Hickenbotham
Peter
P
Friedberg
Errol C
EC
Angulo
Jaime F
JF
Dubrova
Yuri E
YE
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
D004268:DNA-Binding Proteins; D009153:Mutagens; C501002:Xpc protein, mouse; D005038:Ethylnitrosourea