title: [Antioncogene p53 and apoptosis response: new hypotheses on the molecular bases of tumor resistance to radiotherapy].
abstract: Recent experimental data indicate that in normal or neoplastic cells, DNA damage induced by ionizing radiation may work as a signal to trigger apoptosis, a characteristic suicide program inherent to multicellular organisms. The morphological signatures of apoptosis are cell shrinkage, nuclear condensation and genomic fragmentation down to the size of individual nucleosome units (apoptotic bodies). A number of genes have been identified as involved regulators of apoptosis. The tumor suppressor gene p53 has emerged as a main modulator and inducer of apoptosis. Cells containing wild-type p53 function undergo G1 arrest following DNA damage by ionizing radiations. DNA repair processes are, then, activated before the damaged genome can be replicated, with resultant genetic instability. If DNA repair fails, the wild p53 gene may trigger apoptosis and the cell with persisting DNA damage, dies. Cells with loss of functional p53 gene by either gene mutation or deletion appear unable to undergo radiation-induced apoptosis. This evidence may underlie the increased likelihood for p53 deficient cells to develop oncogenetic processes after irradiation exposure. According to p53-triggering apoptosis patterns, cancer cells with a normal p53 gene might be more sensitive to radiotherapy and less proliferating than tumor cells with p53 deficient function. If these data are confirmed, tumors harboring p53 gene mutation might be managed best with particularly aggressive or experimental treatment protocols. Conversely, a higher therapeutic index between malignant and normal cells might be obtained in tumors with fast activation of p53 dependent apoptotic response. Before any definitive conclusions are drawn, further knowledge of the different genes which are known to be involved in the regulation of apoptosis, is warranted.
authors.affiliation: Istituto Nazionale per la Ricerca sul Cancro, Genova.
authors.forename: R
authors.initials: R
authors.lastname: Corvò
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D002455:Cell Division; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009336:Necrosis; D009369:Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D017211:Treatment Failure; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D016159:Tumor Suppressor Protein p53
vernacular_title: Antioncogene p53 e risposta apoptotica: nuove ipotesi sulle basi molecolari della resistenza dei tumori alla radioterapia.