Mechanism of apoptotic resistance of human osteosarcoma cell line, HS-Os-1, against irradiation.
In our previous study, we examined reactive oxygen species (ROS) formation in T lymphocytes following 5 Gy of irradiation. Using a CCD camera system, we monitored fluorescence in T lymphocytes loaded with the succinimidyl ester of Dichlorodihydrofluorescein diacetate (H2DCFDA), which is non-fluorescent until oxidized by ROS. We found that ROS formation occurred immediately after irradiation, continued for several hours, and resulted in oxidative DNA damage. Therefore, the origin of the hyper-radiosensitivity of T lymphocytes seemed to be the high production of ROS in the mitochondrial DNA following irradiation. In this study, we examined radiation-induced ROS formation, oxidative DNA damage, early apoptotic changes, and mitochondrial membrane dysfunction in the human osteosarcoma cell line HS-Os-1, which was established from an osteoblastic tumor that arose in the left humerus of an 11-year-old girl and was already morphologically characterized in vitro and in vivo. We found that ROS formation and oxidative DNA damage were actually scarcely seen after irradiation of up to 30 Gy in these cells; that mitochondrial membrane potential was preserved; and that apoptotic changes were not demonstrated despite the relatively high-dose irradiation of 30 Gy. Therefore, the origin of the close similarity of radiosensitivity between adult articular chondrocytes and the human osteosarcoma cell line HS-Os-1, is considered to involve the low degree of ROS formation following irradiation; the similarity possibly results from the strong scavenging ability of these two kinds of cells for free radicals including hydroxyl radicals.
Ogawa
Yasuhiro
Y
Department of Radiology, Kochi Medical School, Oko-cho, Nankoku-shi, Kochi-Prefecture 783-8505, Japan. ogaway@kochi-ms.ac.jp
Takahashi
Toshiaki
T
Kobayashi
Toshihiro
T
Kariya
Shinji
S
Nishioka
Akihito
A
Mizobuchi
Hiroo
H
Noguchi
Masataka
M
Hamasato
Shinji
S
Tani
Toshikazu
T
Seguchi
Harumichi
H
Yoshida
Shoji
S
Sonobe
Hiroshi
H
D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D002648:Child; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000378:metabolism; D005260:Female; D005452:Fluoresceins / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000494:pharmacology; D005609:Free Radicals; D006801:Humans; D017665:Hydroxyl Radical; D008564:Membrane Potentials; D008856:Microscopy, Fluorescence; D012516:Osteosarcoma / Q000473:pathology* / Q000532:radiotherapy*; D016877:Oxidants / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D017382:Reactive Oxygen Species; D013601:T-Lymphocytes / Q000378:metabolism
C110400:2',7'-dichlorodihydrofluorescein diacetate; D017304:Annexin A5; D004272:DNA, Mitochondrial; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005609:Free Radicals; D016877:Oxidants; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D010100:Oxygen