The dependence of p53 on the radiation enhancement of thermosensitivity at different let.
OBJECTIVE
The aim of this study is to investigate the dependence of p53-gene status on the radiation enhancement of thermosensitivity at different levels of linear energy transfer (LET).


METHODS
We used two kinds of human glioblastoma transfectants of A-172 cells bearing the wild-type p53 gene, A-172/neo cells with control vector containing the neo gene and A-172/mp53 cells with both the dominant negative mutated p53 gene and neo gene. We exposed these cells to X-rays and accelerated carbon-ion (C-) beams (13-200 KeV/microm) followed by heating at 44 degrees C. Cellular sensitivities were determined using clonogenic assay.


RESULTS
The radiation enhancement of thermosensitivity was LET-dependent for the A-172/neo cells, but this was not clearly demonstrated in the A-172/mp53 cells. The supraadditive radiation enhancement of thermosensitivity was observed in A-172/neo cells at the LET range of 13 to 70 KeV/microm, though only an additive effect was observed at higher LET. In A-172/mp53 cells, only an additive effect was observed through all the LET examined.


CONCLUSIONS
These results indicate that the radiation enhancement of thermosensitivity is p53- and LET-dependent. Our results suggest that the combined use of high-LET radiation and hyperthermia brings useful application for cancer therapeutic purposes.
Takahashi
A
A
Department of Biology, Nara Medical University, Nara, Japan.
Ohnishi
K
K
Wang
X
X
Kobayashi
M
M
Matsumoto
H
H
Tamamoto
T
T
Aoki
H
H
Furusawa
Y
Y
Yukawa
O
O
Ohnishi
T
T
D002470:Cell Survival; D003131:Combined Modality Therapy; D016158:Genes, p53 / Q000502:physiology*; D005909:Glioblastoma / Q000235:genetics / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D006979:Hyperthermia, Induced; D018499:Linear Energy Transfer / Q000235:genetics*; D011836:Radiation Tolerance / Q000502:physiology; D011853:Radiobiology; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000528:radiation effects