Induction of apoptosis by high linear energy transfer radiation: role of p53

• Published in: Canadian journal of physiology and pharmacology Vol. 80; no. 7; pp. 644 - 649
• Main Authors: Coelho, D, Fischer, B, Holl, V, Dufour, P, Denis, J M, Gueulette, J, Bergerat, J P, Bischoff, P
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Ottawa, Canada NRC Research Press 01.07.2002; National Research Council of Canada; Canadian Science Publishing NRC Research Press
• Subjects: Apoptosis; Biological and medical sciences; Medical sciences; Physiological aspects; Radiation; Radiation therapy and radiosensitizing agent; Treatment with physical agents; Treatment. General aspects; Tumors; Human; Radiosensitivity; Lymphoblast; Radiotherapy; In vitro; Linear energy transfer; Cell line; TP53 Gene; Physical agent; Cell death; Fast neutron; Lymphoblastoid cell; Tumor cell; Apoptosis
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/y02-072

The involvement of the tumor suppressor p53 gene in the sensitivity of many cell types towards low linear energy transfer (LET) radiation is now well established. However, little information is available on the relationship between p53 status of tumor cells and their ability to undergo apoptosis following exposure to high-LET radiation. Here we present the results of experiments carried out with the human lymphoblastoid cell line TK6 and its p53 knock-out counterpart NH32. Cells were irradiated at doses ranging from 0.25 to 8 Gy with fast neutrons (65 MeV), carbon ions (95 MeV/nucleon), and X rays (15 MV). For both cell lines, the occurrence of apoptosis, determined by the quantification of hypodiploid particles as well as the activation of several caspases, was compared with their sensitivity towards high-LET radiation. Results indicate that p53 is involved in the response of TK6 cells to fast neutrons and carbon ions, as measured by cell proliferation and occurrence of apoptosis. However, p53-deficient cells are still able to undergo apoptosis following irradiation. This suggests that heavy ions and fast neutrons induce cellular damage that is not under the control of p53. The involvement of executioner caspases in high-LET radiation induced apoptosis was also evaluated by use of specific inhibitors.Key words: fast neutrons, carbon ions, apoptosis, p53, lymphoblastoid cell line.