title: Expression of different mutant p53 transgenes in neuroblastoma cells leads to different cellular responses to genotoxic agents.
abstract: The involvement of p53 as a determinant of chemosensitivity or radiosensitivity is not well understood and is complicated by numerous contradictory reports. Here we have addressed this issue using a series of isogenic clones derived from two neuroblastoma cell lines that express wild-type p53 genes, Nub7 and IMR32. Two different mutant p53 transgenes were used in an attempt to disrupt p53 function in the clones. Our findings indicate that the cellular response is dependent on the genotoxic agent used as well as on the specific p53 transgene used. Cellular radiosensitivity showed no association with apoptosis or with the ability of the cells to arrest in G1 after irradiation. An association was observed, however, between gamma-radiation sensitivity and DNA double-strand break rejoining activity.
authors.affiliation: Ontario Cancer Institute, Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada.
authors.forename: Suman
authors.initials: S
authors.lastname: Gangopadhyay
authors.forename: Farid
authors.initials: F
authors.lastname: Jalali
authors.forename: Danny
authors.initials: D
authors.lastname: Reda
authors.forename: Jim
authors.initials: J
authors.lastname: Peacock
authors.forename: Robert G
authors.initials: RG
authors.lastname: Bristow
authors.forename: Samuel
authors.initials: S
authors.lastname: Benchimol
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005047:Etoposide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000528:radiation effects; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009447:Neuroblastoma / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics; D019076:Transgenes; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; D002945:Cisplatin