| First Author | Aubrecht J | Year | 1999 |
| Journal | Carcinogenesis | Volume | 20 |
| Issue | 12 | Pages | 2229-36 |
| PubMed ID | 10590213 | Mgi Jnum | J:59211 |
| Mgi Id | MGI:1351162 | Doi | 10.1093/carcin/20.12.2229 |
| Citation | Aubrecht J, et al. (1999) Involvement of p53 in X-ray induced intrachromosomal recombination in mice. Carcinogenesis 20(12):2229-36 |
| abstractText | 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 benzoapyrene (BaP; 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, BaP 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 BaP 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. |
