The combined effects of xeroderma pigmentosum C deficiency and mutagens on mutation rates in the mouse germ line

Laurent Miccoli, Karen L A Burr, Peter Hickenbotham, Errol C. Friedberg, Jaime F. Angulo, Yuri E. Dubrova

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12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4695-4699
Number of pages5
JournalCancer Research
Volume67
Issue number10
DOIs
StatePublished - May 15 2007

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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