Radiation-induced apoptosis in human tumor cell lines: adaptive response and split-dose effect.
Irradiation of human ovarian carcinoma cells (OVCAR 3) and myeloma cells (RPMI 8226) with graded doses of 137Cs-gamma-rays led to a 35-40% increase in time-dependent apoptosis 72 hr after 6-8 Gy irradiation. Large individual variations in sensitivity to radiation-induced apoptosis were noted in human lymphocytes obtained from 5 donors. Pretreatment of OVCAR 3 and RPMI 8226 cells with 0.01 Gy increased their resistance to apoptosis after subsequent 6 Gy irradiation several hours or 48 and 72 hr later. A dose of 4 or 8 Gy given in 2 equal fractions at an interval of a few hours produced a low level of apoptosis compared to that resulting from a single administration of the same total dose. Adaptive response was demonstrated in 2 out of 3 samples of human lymphocytes isolated from different donors, and no split-dose effect for apoptosis was noted in 2 other donors. In split-dose experiments, there was no correlation between the sensitivity of cells to apoptosis and their position in the cell cycle, after the first half-dose. No G1 block was observed in irradiated cell lines. Adaptive response and split-dose effect were prevented by 3-aminobenzamide and okadaic acid which inhibit poly(ADP-ribose)polymerase and protein phosphatase, respectively. These results imply a common mechanism for acquired resistance to radiation-induced apoptosis in adaptive response and the split-dose effect.
Filippovich
I V
IV
Radiobiology Group, INSERM Research Unit 463, Institute of Biology, Nantes, France.
Sorokina
N I
NI
Robillard
N
N
Lisbona
A
A
Chatal
J F
JF
D017209:Apoptosis / Q000528:radiation effects*; D002277:Carcinoma / Q000473:pathology* / Q000532:radiotherapy; D005260:Female; D006801:Humans; D009101:Multiple Myeloma / Q000473:pathology* / Q000532:radiotherapy; D010051:Ovarian Neoplasms / Q000473:pathology* / Q000532:radiotherapy; D011829:Radiation Dosage; D013997:Time Factors; D014407:Tumor Cells, Cultured