Bystander cell death and stress response is inhibited by the radical scavenger α(1)-microglobulin in irradiated cell cultures.
Alpha-particle irradiation of cells damages not only the irradiated cells but also nontargeted bystander cells. It has been proposed that the bystander effect is caused by oxidants and free radicals generated by the radiation. Recent studies have shown that α(1)-microglobulin protects against cell damage caused by oxidants and free radicals. Using a novel experimental system that allows irradiation of 0.02% of a human hepatoma monolayer, leaving 99.98% as bystander cells, we investigated the influence of oxidative stress and the cell-protective effects of α(1)-microglobulin during α-particle irradiation. The results showed an increase in cell death in both irradiated cells and bystander cells. A significant increase in apoptosis, oxidation markers and expression of the stress response genes heme oxygenase 1, superoxide dismutase, catalase, glutathione peroxidase 1, p21 and p53 were observed. Addition of α(1)-microglobulin reduced the amount of dead cells and inhibited apoptosis, formation of oxidation markers, and up-regulation of stress response genes. The results emphasize the role of oxidative stress in promoting bystander effects. Furthermore, the results suggest that α(1)-microglobulin protects nonirradiated cells by eliminating oxidants and free radicals generated by radiation and imply that α(1)-microglobulin can be used in radiation therapy of tumors to minimize damage to surrounding tissues.
Division of Infection Medicine, Lund University, Lund, Sweden.
Magnus G
MG
Olsson
E J Charlotta
EJ
Nilsson
Sigurbjörg
S
Rutardóttir
Jan
J
Paczesny
Jan
J
Pallon
Bo
B
Akerström
D000512:Alpha Particles; D000510:Alpha-Globulins / Q000378:metabolism / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D024201:Bystander Effect / Q000187:drug effects* / Q000528:radiation effects*; D016923:Cell Death / Q000187:drug effects* / Q000528:radiation effects*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D016166:Free Radical Scavengers / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects*; D021381:Protein Transport / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects
D000510:Alpha-Globulins; D015415:Biomarkers; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C016001:alpha-1-microglobulin