Induction of bystander response in human glioma cells using high-energy electrons: a role for TGF-beta1.
We examined bystander cell death produced in T98G cells by exposure to irradiated cell conditioned medium (ICCM) produced by high-energy 20 MeV electrons at a dose rate of 10 Gy min(-1) and doses up to 20 Gy. ICCM induced a bystander response in T98G glioma cells, reducing recipient cell survival by more than 25% below controls at 5 and 10 Gy. Higher doses increased survival to near control levels. ICCM was analyzed for the presence of transforming growth factor alpha (TGF-alpha) and transforming growth factor beta1 (TGF-beta1). Monoclonal antibodies for TGF-alpha (mAb TGF-alpha) and TGF-beta1 (mAb TGF-beta1) were added to the ICCM to neutralize any potential effect of the cytokines. The results indicate that TGF-alpha was not present in the ICCM and addition of mAb TGF-alpha to the ICCM had no effect on bystander cell survival. No active TGF-beta1 was present in the ICCM; however, addition of mAb TGF-beta1 completely abolished bystander death of reporter cells at all doses. These results indicate that bystander cell death can be induced in T98G glioma if a large enough radiation stress is applied and that TGF-beta1 plays a downstream role in this response.
Gow
M D
MD
Medical Physics and Applied Radiation Sciences Department, McMaster University, Hamilton, Ontario, Canada L8S 4K1.
Seymour
C B
CB
Ryan
L A
LA
Mothersill
C E
CE
D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D024201:Bystander Effect / Q000528:radiation effects*; D016923:Cell Death / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D017077:Culture Media, Conditioned / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D004583:Electrons; D005910:Glioma / Q000473:pathology*; D006801:Humans; D016211:Transforming Growth Factor alpha / Q000276:immunology / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D017077:Culture Media, Conditioned; D016211:Transforming Growth Factor alpha; D053773:Transforming Growth Factor beta1