Cytotoxic enhancement of low dose-rate irradiation in human lung cancer cells by mild hyperthermia.
OBJECTIVE
The aim of this study was to investigate the cell killing induced by low dose-rate irradiation (LDRI) simultaneously combined with long duration mild hyperthermia in LK87 human lung cancer cells. Cell cycle alteration due to this combined treatment was also observed.


METHODS
Human lung adenocarcinoma cells, LK87, were treated with concurrent LDRI (50 cGy/hr) and mild hyperthermia (38 to 42 degrees C). Cell survival was estimated by clonogenic assay. Flow cytometry was performed with FACScan. The treatments were simultaneously performed for up to 48 hr (24 Gy).


RESULTS
Survival curves of mild hyperthermia alone revealed development of chronic thermotolerance up to 48 hr, whereas LDRI plus hyperthermia caused an exponential decrease in survival. The LDRI cytotoxicities were enhanced by mild hyperthermia over a non-lethal temperature range. The Do values calculated from dose response curves at 37, 38, 39, 40, 41 41.5 and 42 degrees C were 6.55, 5.25, 4.24, 3.99, 3.46, 1.83 and 0.70 Gy, respectively. Cell cycle analysis demonstrated a remarkable G2 and a mild G1 block for LDRI alone, but only a G1 block was observed for LDRI combined with 41 degrees C hyperthermia.


CONCLUSIONS
The LDRI cytotoxicity was enhanced by long duration mild temperature hyperthermia. The suppression of chronic thermotolerance was considered to be a mechanism involved in this sensitization.
Sakurai
H
H
Department of Radiology and Radiation Oncology, Gunma University School of Medicine, Japan. hsakurai@sb.gunma-u.ac.jp
Mitsuhashi
N
N
Kitamoto
Y
Y
Nonaka
T
T
Harashima
K
K
Higuchi
K
K
Muramatsu
H
H
Ebara
T
T
Ishikawa
H
H
Niibe
H
H
D002470:Cell Survival / Q000502:physiology* / Q000528:radiation effects; D002588:Cesium Radioisotopes; D004273:DNA, Neoplasm / Q000032:analysis / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D006358:Hot Temperature; D006801:Humans; D006979:Hyperthermia, Induced; D008175:Lung Neoplasms; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D002588:Cesium Radioisotopes; D004273:DNA, Neoplasm