Journal Article

Involvement of p53 in X-ray induced intrachromosomal recombination in mice

Jiri Aubrecht, M.Béatrice Secretan, Alexander J.R. Bishop and Robert H. Schiestl

in Carcinogenesis

Volume 20, issue 12, pages 2229-2236
Published in print December 1999 | ISSN: 0143-3334
Published online December 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.12.2229
Involvement of p53 in X-ray induced intrachromosomal recombination in mice

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The tumor suppressor gene Trp53 (also known as p53) is the most frequently mutated gene in human cancers. p53 is induced in response to DNA damage and effects a G1 cell cycle arrest. It is believed that p53 plays a key role in maintaining genomic integrity following exposure to DNA-damaging agents. We determined the frequency of spontaneous and DNA damage-induced homologous intrachromosomal recombination in p53-deficient mouse embryos. Homologous intrachromosomal recombination events resulting in deletions at the pink eyed unstable (pun) locus result in reversion to the p gene. Reversions occurring in embryonic premelanocytes give rise to black spots on the gray fur of the offspring. Pregnant C57BL/6J pun/pun p53+/– mice were exposed to X-rays (1 Gy) or administered benzo[a]pyrene (B[a]P; 30 or 150 mg/kg i.p.) 10 days after conception. Frequencies of spontaneous pun reversions in p53–/– and p53+/– animals were not significantly different compared with their wild-type littermates. X-ray treatment increased the recombination frequency in wild-type and p53+/–, but surprisingly not in p53–/– offspring. In contrast, B[a]P treatment caused a dose-dependent increase in pun reversion frequencies in all three genotypes. Western blot analysis of embryos indicated that p53 protein levels increased ~3-fold following X-ray treatment, while B[a]P had no effect on p53 expression. These results are in agreement with the proposal that p53 is involved in the DNA damage response following X-ray exposure and suggest that X-ray-induced double-strand breaks are processed differently in p53–/– animals.

Keywords: B[a]P, benzo[a]pyrene; DSB, double-strand break.

Journal Article.  7111 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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