title: p53 status and its in vitro relationship to radiosensitivity and chemosensitivity in lung cancer.
abstract: The following study was designed to investigate if mutations within the p53 gene are associated with radiation responsiveness or response to different cytotoxic drugs. Nine human lung cancer cell lines were examined (four SCLC and five NSCLC cell lines). cDNA-based sequencing of the entire p53 gene was performed. All cell lines were characterised with respect to drug-sensitivity towards eight cytotoxic drugs using the FMCA method and data from the clonogenic assay were studied to obtain information concerning radioresponsiveness. All the cell lines expressed mutations; six were missense mutations and three were deletions. A statistically significant increase in radiosensitivity was found for mutations in exon 7 (p = 0.019), compared with the other mutations localised within different exons of p53. Further statistical analyses using Fisher's two-tailed exact test confirmed that mutations in exon 7 were significantly associated with radiosensitivity, p = 0.047. No correlation concerning mutations in separate exons and response towards different chemotherapeutic agents could be found. Our results indicate that p53 mutations in exon 7 might be associated with increased radiation sensitivity in these human lung cancer cell lines, but our data should be interpreted with caution since several other explanations might exist regarding what determines the response towards radiation.
authors.affiliation: Department of Oncology, Radiology and Clinical Immunology, Uppsala University Hospital, 751 85 Uppsala, Sweden. Michael.Bergqvist@onkologi.uu.se
authors.forename: Michael
authors.initials: M
authors.lastname: Bergqvist
authors.forename: Daniel
authors.initials: D
authors.lastname: Brattström
authors.forename: Joachim
authors.initials: J
authors.lastname: Gullbo
authors.forename: Patrik
authors.initials: P
authors.lastname: Hesselius
authors.forename: Ola
authors.initials: O
authors.lastname: Brodin
authors.forename: Gunnar
authors.initials: G
authors.lastname: Wagenius
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology; D017338:Cladribine / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D000077143:Docetaxel; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008558:Melphalan / Q000494:pharmacology; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology; D011836:Radiation Tolerance / Q000235:genetics*; D017384:Sequence Deletion; D043823:Taxoids; D019772:Topotecan / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D014410:Tumor Stem Cell Assay; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D014747:Vinblastine / Q000494:pharmacology
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D043823:Taxoids; D016159:Tumor Suppressor Protein p53; D003561:Cytarabine; D000077143:Docetaxel; D017338:Cladribine; D014747:Vinblastine; D019772:Topotecan; D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin; D008558:Melphalan