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Radiation‐induced apoptosis in human tumor cell lines: Adaptive response and split‐dose effect
Author(s) -
Filippovich Igor V.,
Sorokitalya I.,
Robillard Nelly,
Lisbona Albert,
Chatal JeanFrançois
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980703)77:1<76::aid-ijc13>3.0.co;2-7
Subject(s) - apoptosis , irradiation , cell culture , poly adp ribose polymerase , ionizing radiation , biology , radiation sensitivity , cancer research , medicine , andrology , microbiology and biotechnology , immunology , polymerase , biochemistry , physics , genetics , nuclear physics , gene
Irradiation of human ovarian carcinoma cells (OVCAR 3) and myeloma cells (RPMI 8226) with graded doses of 137 Cs‐γ‐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 G 1 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. Int. J. Cancer 77:76–81, 1998.© 1998 Wiley‐Liss, Inc.