Isolation and characterization of highly radioresistant malignant hamster fibroblasts that survive acute gamma irradiation with 20 Gy.
To study the acquired radioresistance of tumor cells, a model system of two cell lines, Djungarian hamster fibroblasts (DH-TK-) and their radioresistant progeny, was established. The progeny of irradiated cells were isolated by treating the parental cell monolayer with a single dose of 20 Gy (PIC-20). The genetic and morphological features, clonogenic ability, radiosensitivity, cell growth kinetics, ability to grow in methylcellulose, and tumorigenicity of these cell lines were compared. The plating efficiency of PIC-20 cells exceeded that of DH-TK- cells. The progeny of irradiated cells were more radioresistant than parental cells. The average D0 for PIC-20 cells was 7.4 +/- 0.2 Gy, which is three times higher than that for parental cells (2.5 +/- 0.1 Gy). Progeny cell survival in methylcellulose after irradiation with a dose of 10 Gy was 15 times higher than that of DH-TK- cells. In contrast to parental cells, the progeny of irradiated cells showed fast and effective repopulation after irradiation with doses of 12.5 and 15 Gy. The tumor formation ability of irradiated progeny cells was higher than that of parental cells; after 15 Gy irradiation, PIC-20 cells produced tumors as large as unirradiated progeny of irradiated cells, whereas the tumor development of DH-TK- cells diminished by 70%. High radioresistance of progeny of irradiated cells was reproduced during the long period of cultivation (more than 80 passages). The stability of the radioresistant phenotype of PIC-20 cells allows us to investigate the possible mechanisms of acquired tumor radioresistance.
Tyrsina
Ekaterina G
EG
Institute of Carcinogenesis of Russian Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478, Russia. Katt@newmail.ru
Slanina
Svetlana V
SV
Kakpakova
Evgeniya S
ES
Kalendo
Galina S
GS
Kan
Natalia G
NG
Tyrsin
Oleg Y
OY
Ryskov
Alexei P
AP
D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division; D045744:Cell Line, Tumor; D048429:Cell Size; D002470:Cell Survival / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects; D003260:Contact Inhibition; D006224:Cricetinae; D016172:DNA Fingerprinting; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology / Q000528:radiation effects*; D005720:Gamma Rays; D007700:Kinetics; D009368:Neoplasm Transplantation; D011836:Radiation Tolerance