High-LET radiation enhanced apoptosis but not necrosis regardless of p53 status.
OBJECTIVE
We analyzed the death pattern of human lung cancer cells harboring different p53 statuses after irradiation with different levels of linear energy transfer (LET).


METHODS
We used three kinds of human lung cancer cell lines with identical genotypes, except for the p53 gene. These cells were exposed to X-rays or accelerated carbon-ion beams. The cellular sensitivities were determined by a colony-forming assay. The detection and quantification of cell death (apoptosis and necrosis) were evaluated and compared by acridine orange/ethidium bromide double staining for fluorescence microscopy.


RESULTS
We found that (1) there was no significant difference in cellular sensitivity to LET radiation >70 KeV/microm, although wild-type p53 cell sensitivity to X-rays was higher than that of mutated p53 or p53-null cells; (2) low-LET radiation effectively induced apoptosis in wild-type p53 cells as compared with mutated p53 and p53-null cells; and (3) high-LET radiation induced p53-independent apoptosis.


CONCLUSIONS
Our findings suggest that high-LET radiotherapy is expected to be a valid application for patients carrying mutated p53 cancer cells. We proposed that the elucidation of the p53-independent apoptosis-related genes might provide new insights into radiotherapy for cancer.
Takahashi
Akihisa
A
Department of Biology, Nara Medical University, Nara, Japan.
Matsumoto
Hideki
H
Yuki
Kazue
K
Yasumoto
Jun-Ichi
J
Kajiwara
Atsuhisa
A
Aoki
Mizuho
M
Furusawa
Yoshiya
Y
Ohnishi
Ken
K
Ohnishi
Takeo
T
D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000532:radiotherapy; D002470:Cell Survival / Q000528:radiation effects; D016158:Genes, p53; D006801:Humans; D018499:Linear Energy Transfer; D008175:Lung Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D009336:Necrosis; D011836:Radiation Tolerance / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D014410:Tumor Stem Cell Assay