title: Gene expression and apoptosis induction in p53-heterozygous irradiated mice.
abstract: The role of the p53-genetic background in the expression of genes involved in either cell cycle checkpoint activation or apoptosis was evaluated in p53+/+ and p53+/- mouse strains at both basal levels and after DNA-induced damage. The spleen, colon, kidneys, lungs and liver of both strains were harvested from untreated animals and from mice exposed to 7.5 Gy of X-rays and sacrificed after 5 h. No significant differences were observed in the basal levels of p53 protein, CDKN1A and bax mRNA and spontaneous apoptosis, neither among the different organs within the same strain, nor between the same organ in the p53+/+ and p53+/- strains. After X-ray exposure, p53-dependent regulation was strikingly tissue-specific. In wild-type irradiated mice, p53 protein level increased after radiation treatment in all the organs analysed, whereas both CDKN1A and bax genes transcription increased in the spleen, colon and lungs, as assessed by means of quantitative RT-PCR. In p53+/- irradiated mice, on the contrary, a significant p53 induction was detected only in the spleen, while CDKN1A and bax genes levels increased in the spleen, colon and lungs, revealing the existence of different mechanisms of gene regulation in different organs. Apoptosis induction was observed in the spleen and colon of both strains, even if to lower extent in p53+/- mice compared to p53+/+ animals. In conclusion, in the spleen and colon, target gene transcription and apoptosis may be related to p53 genotype after DNA damage-induction. Moreover, our findings highlight the selectivity of p53 in transactivation following DNA damage in vivo, resulting in tissue-specific responses.
authors.affiliation: Department of Biology, University of Rome Roma Tre, Viale G. Marconi, 446, 00146 Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: di Masi
authors.forename: Antonio
authors.initials: A
authors.lastname: Antoccia
authors.forename: Ivan
authors.initials: I
authors.lastname: Dimauro
authors.forename: Alberta
authors.initials: A
authors.lastname: Argentino-Storino
authors.forename: Alberto
authors.initials: A
authors.lastname: Mosiello
authors.forename: Ruggiero
authors.initials: R
authors.lastname: Mango
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.forename: Caterina
authors.initials: C
authors.lastname: Tanzarella
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D002453:Cell Cycle / Q000528:radiation effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D053938:DNA Fragmentation / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006580:Genetic Carrier Screening; D006720:Homozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics* / Q000528:radiation effects; D014965:X-Rays; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein