Differential induction of apoptosis in x-irradiated L5178Y sublines bearing p53 mutation.
We examined apoptosis and expression of p53, E2F-1, bax, bclx(L) and bc12 proteins in two L5178Y (LY) murine lymphoma sublines, LY-R and LY-S, which differ in radiosensitivity and double-strand break (DSB) repair. Both sublines are heterozygous for a p53 mutation in codon 170 that precludes the transactivation function. Accordingly, there is no G1/S arrest after irradiation. We found that there is no change in expression of E2F-1, bax, bclx(L) or bc12 proteins in both LY sublines after x-irradiation. LY-R cells do not constitutively express bc12, whereas both sublines show high bax content. Radiation induces delayed apoptosis to a greater extent in LY-S than in LY-R cells. The apoptosis can be seen 24 h after irradiation (2 Gy) of LY-S cells, with a maximum at 48 h. LY-R cells need 5 Gy and 72 h post-irradiation incubation to show marked apoptosis (identified by the TUNEL method). The reported observations support the assumption that differential radiosensitivity of LY sublines is associated with the induction of apoptosis that is not related to transactivation by p53 and is primarily related to differential DNA repair ability.
Szumiel
I
I
Department of Radiobiology and Health Protection, Institute of Nuclear Chemistry and Technology, Warsaw, Poland. izasz@orange.ichtj.waw.pl
Jaworska
A
A
Kapiszewska
M
M
John
A
A
Gradzka
I
I
Sochanowicz
B
B
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002352:Carrier Proteins; D002453:Cell Cycle / Q000528:radiation effects; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D016158:Genes, p53 / Q000235:genetics; D007940:Leukemia L5178; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D011836:Radiation Tolerance; D056465:Retinoblastoma-Binding Protein 1; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured; D014965:X-Rays; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D056465:Retinoblastoma-Binding Protein 1; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein