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Mutat Res ; 757(2): 114-9, 2013 Oct 09.
Article in English | MEDLINE | ID: mdl-23906726

ABSTRACT

To determine whether the bleomycin (BLM)-induced bystander response occurs in human brain glioblastoma (BMG-1) cells, the BMG-1 cells were exposed to two different concentrations of BLM. The co-culture methodology was adopted to study the in vitro bystander effects. DNA damage was measured using the micronucleus (MN) and γ-H2AX assays. Cytotoxicity was measured using the trypan blue assay. Cell cycle kinetics was analyzed using flow cytometry. The overall results did not show any significant increase in either genotoxicity or cytotoxicity or a delay in the cell cycle kinetics in BMG-1 bystander cells co-cultured with BLM-exposed cells, suggesting that BLM did not induce a bystander response in the BMG-1 cells. Furthermore, the MN results of the BLM-exposed BMG-1 cells co-cultured with unexposed bystander human lung adenocarcinoma (A549 and NCI-H460) cells and vice versa suggested that the BMG-1 cells do not secrete bystander signals but do respond to those signals. Analyzing the underlying mechanism and pathways involved in preventing the cells from secreting bystander signals will provide new insights that can be applied to inhibit these mechanisms in other cell types, thereby preventing and controlling the bystander response and genomic instability and increasing the therapeutic gain in chemotherapy.


Subject(s)
Adenocarcinoma/metabolism , Antibiotics, Antineoplastic/pharmacology , Bleomycin/pharmacology , Brain Neoplasms/metabolism , Bystander Effect/drug effects , Glioblastoma/metabolism , Lung Neoplasms/metabolism , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Antibiotics, Antineoplastic/therapeutic use , Bleomycin/therapeutic use , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Cell Line, Tumor , Coculture Techniques , Female , Genomic Instability/drug effects , Glioblastoma/drug therapy , Glioblastoma/pathology , Histones/metabolism , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Male , Neoplasm Proteins/metabolism , Signal Transduction/drug effects
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