p53-dependent thermal enhancement of cellular sensitivity in human squamous cell carcinomas in relation to LET

Citation
A. Takahashi et al., p53-dependent thermal enhancement of cellular sensitivity in human squamous cell carcinomas in relation to LET, INT J RAD B, 77(10), 2001, pp. 1043-1051
Citations number
47
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Experimental Biology
Journal title
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
ISSN journal
0955-3002 → ACNP
Volume
77
Issue
10
Year of publication
2001
Pages
1043 - 1051
Database
ISI
SICI code
0955-3002(200110)77:10<1043:PTEOCS>2.0.ZU;2-S
Abstract
Purpose: To investigate the dependence on p53 gene status of the thermal en hancement of cellular sensitivity against different levels of linear energy transfer (LET) from X-rays or carbon-ion (C-) beams. Materials and methods: Two kinds of human squamous cell carcinoma cell line s were used with an identical genotype except for the p53 gene. SAS/mp53 ce lls were established by transfection with mutated p53 (mp53) gene to SAS ce lls having functional wild-type p53 (wtp53). As the control, a neo vector w as transfected to the SAS cells (SAS/neo cells). Both cells were exposed to X-rays or accelerated C-beams (30-150 KeV mum(-1)) followed by heating at 44 degreesC. Cellular sensitivity was determined by colony-forming activity . Induction of apoptosis was analysed by Hoechst 33342 staining of apoptoti c bodies and agarose-gel electrophoresis for the formation of DNA ladders. Results: It was found that (1) there was no significant difference in cellu lar sensitivity between SAS/neo and SAS/mp53 cells to LET radiation of >30 KeV mum(-1), although the radiosensitivity of SAS/neo cells to X-rays was h igher (1.2-fold) than that of SAS/mp53 cells; (2) there was an interactive thermal enhancement of radiosensitivity below an LET of 70 KeV mum(-1) in S AS/neo cells, although only additive thermal enhancement was observed in AS /mp53 cells through all LET levels examined; (3) low-LET radiation induced apoptosis only in SAS/neo cells; (4) high-LET radiation at an isosurvival d ose-induced apoptosis of SAS/neo cells at a higher frequency compared with that with low-LET radiation; (5) high-LET radiation-induced p53-independent apoptosis in SAS/mp53 cells; and (6) thermal enhancement of cellular sensi tivity to X-rays was due to induction of p53-dependent apoptosis. Conclusions: The findings suggest that thermal enhancement of radiosensitiv ity may result from p53-dependent apoptosis induced by inhibition of p53-de pendent cell survival system(s) through either regulation of the cell cycle or induction of DNA repair. It is also suggested that the analysis of p53 gene status of cancer cells may predict response to combined therapies with low-LET radiation and hyperthermia.