title: The cisplatin-irradiation combination suggests that apoptosis is not a major determinant of clonogenic death.
abstract: It is commonly believed that tumor cells treated with anticancer agents, chemotherapy and/or radiation, die by apoptosis and that tumors which do not undergo apoptosis are resistant to treatment. In this study, we investigated the molecular basis underlying cisplatin cytotoxicity in the murine teratocarcinoma F9 cell line to see whether irradiation enhances cisplatin-induced cytotoxicity. We compared the apoptosis induced by chemo and/or radiotherapy with other cellular effects such as cell survival, clonogenic capability, cell cycle perturbation, expression of p53 and p53-related mRNAs, and necrosis. When combined with radiation, a clear additive cytotoxic effect of cisplatin was demonstrated. We found that both cisplatin and radiation induced cell death, but the level of induced apoptosis was low and there was no correlation with the results of the clonogenic assays: we noted a difference between cytotoxic effects in the clonogenic assay and the extent of apoptosis by fluorescence-activated cell sorter analysis, suggesting that cell killing reflected not only apoptosis but also cell cycle arrest, and that apoptosis, cell kinetics and clonogenicity suppression were independent processes.
authors.affiliation: Molecular Biology Unit, Azienda Ospedaliera S. Croce e Carle, Cuneo, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Lo Nigro
authors.forename: Elena
authors.initials: E
authors.lastname: Arnolfo
authors.forename: Enrico
authors.initials: E
authors.lastname: Taricco
authors.forename: Adriana
authors.initials: A
authors.lastname: Fruttero
authors.forename: Elvio Grazioso
authors.initials: EG
authors.lastname: Russi
authors.forename: Francesco
authors.initials: F
authors.lastname: Lucio
authors.forename: Silvana
authors.initials: S
authors.lastname: Ribero
authors.forename: Alberto
authors.initials: A
authors.lastname: Comino
authors.forename: Marco
authors.initials: M
authors.lastname: Merlano
authors.forename: Silvana
authors.initials: S
authors.lastname: Ungari
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000494:pharmacology*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D009336:Necrosis; D012333:RNA, Messenger / Q000235:genetics; D011839:Radiation, Ionizing; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014410:Tumor Stem Cell Assay; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin