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Radiation-induced apoptosis in human tumor cell lines: adaptive response and split-dose effect
I V Filippovich1, N I Sorokina, N Robillard
1Radiobiology Group, INSERM Research Unit 463, Institute of Biology, Nantes, France.
International Journal of Cancer
|June 25, 1998
Summary
Low-dose radiation can induce resistance to apoptosis in cancer cells, a phenomenon observed in both cell lines and human lymphocytes. This adaptive response and split-dose effect suggest a shared underlying mechanism in radiation resistance.
Area of Science:
- Radiobiology
- Cellular Biology
- Cancer Research
Background:
- Radiation therapy is a cornerstone of cancer treatment.
- Understanding cellular responses to radiation, such as apoptosis, is crucial for optimizing treatment efficacy.
- Individual variations in cellular sensitivity to radiation exist, necessitating further investigation into resistance mechanisms.
Purpose of the Study:
- To investigate the phenomenon of adaptive response and split-dose effect on radiation-induced apoptosis in human cancer cell lines and lymphocytes.
- To explore the potential common mechanisms underlying acquired resistance to apoptosis.
- To examine the role of poly(ADP-ribose)polymerase and protein phosphatase in these radiation responses.
Main Methods:
- Irradiation of human ovarian carcinoma (OVCAR 3) and myeloma (RPMI 8226) cells with graded doses of 137Cs-gamma-rays.
- Assessment of time-dependent apoptosis 72 hours post-irradiation.
- Evaluation of adaptive response and split-dose effects using varying irradiation fractionation.
- Inhibition studies using 3-aminobenzamide and okadaic acid.
Main Results:
- A 35-40% increase in apoptosis was observed 72 hours after 6-8 Gy irradiation in OVCAR 3 and RPMI 8226 cells.
- Pre-irradiation with 0.01 Gy induced resistance to subsequent higher doses of radiation.
- Split-dose irradiation resulted in lower apoptosis levels compared to single doses.
- Adaptive response was observed in lymphocytes from 2 out of 3 donors.
- Inhibition of poly(ADP-ribose)polymerase and protein phosphatase prevented adaptive response and split-dose effects.
Conclusions:
- Acquired resistance to radiation-induced apoptosis, observed in adaptive response and split-dose effects, likely shares a common molecular mechanism.
- Poly(ADP-ribose)polymerase and protein phosphatase play critical roles in mediating these resistance phenomena.
- Findings suggest potential strategies to modulate cellular sensitivity to radiation therapy.