Spontaneous and radiation-induced apoptosis in lung carcinoma cells with different intrinsic radiosensitivities.
Spontaneous and radiation-induced apoptosis in three lung carcinoma cell lines (U-1285, U-1906 and U-1810) with previously characterised intrinsic radiosensitivities (RS) was assessed by TUNEL-staining, detection of DNA laddering and cleavage of poly-(ADP-ribose) polymerase (PARP). Spontaneous apoptosis was detected at a high level in the radiosensitive U-1285, at an intermediate level in U-1906 and not detected in the radioresistant U-1810 cell line. Radiation-induced apoptosis, assessed by TUNEL assay, was present in U-1285 and U-1906 cells but not in U-1810 cells. To explain these findings, expression of Bcl-2, Bax, c-Myc and RB protein and mutations of the p53 gene were analysed. The ratio Bcl-2/Bax was higher in U-1810 cells compared with U-1285 and U-1906 cells. Overexpression of c-Myc and loss of RB was found in U-1285 cells whereas both U-1906 and U-1810 cells expressed RB and showed lower c-Myc expression. Analysis with sequencing of all p53 exons disclosed mutations in all three cell lines. Thus, apoptosis was a p53 independent process in U-1285 and U-1906 cells. RB loss and overexpression of c-Myc may enhance apoptosis in U-1285 cells. Our data suggest that spontaneous apoptosis may correlate with RS in SCLC.
Sirzén
F
F
Department of Oncology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
Zhivotovsky
B
B
Nilsson
A
A
Bergh
J
J
Lewensohn
R
R
D017209:Apoptosis / Q000528:radiation effects; D053938:DNA Fragmentation; D016259:Genes, myc; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured
D019253:Proto-Oncogene Proteins c-bcl-2