title: Involvement of p53 in X-ray induced intrachromosomal recombination in mice.
abstract: 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 G(1) 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 (p(un)) 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 p(un)/p(un) p53(+/-) mice were exposed to X-rays (1 Gy) or administered benzo¿apyrene (B¿aP; 30 or 150 mg/kg i.p.) 10 days after conception. Frequencies of spontaneous p(un) 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¿aP treatment caused a dose-dependent increase in p(un) reversion frequencies in all three genotypes. Western blot analysis of embryos indicated that p53 protein levels increased approximately 3-fold following X-ray treatment, while B¿aP 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.
authors.affiliation: Department of Cancer Cell Biology, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 2115, USA.
authors.forename: J
authors.initials: J
authors.lastname: Aubrecht
authors.forename: M B
authors.initials: MB
authors.lastname: Secretan
authors.forename: A J
authors.initials: AJ
authors.lastname: Bishop
authors.forename: R H
authors.initials: RH
authors.lastname: Schiestl
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D017353:Gene Deletion; D016158:Genes, p53; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011995:Recombination, Genetic / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects*
chemical_list: D002273:Carcinogens; D001564:Benzo(a)pyrene