title: Human brain glioblastoma cells do not induce but do respond to the bleomycin-induced bystander response from lung adenocarcinoma cells.
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.
authors.affiliation: Department of Human Genetics, College of Biomedical Science Technology and Research, Sri Ramachandra University, Porur, Chennai 600 116, India.
authors.forename: Safa Abdul Syed
authors.initials: SA
authors.lastname: Basheerudeen
authors.forename: Chinnadurai
authors.initials: C
authors.lastname: Mani
authors.forename: Megha Anil Kumar
authors.initials: MA
authors.lastname: Kulkarni
authors.forename: Karthika
authors.initials: K
authors.lastname: Pillai
authors.forename: Anila
authors.initials: A
authors.lastname: Rajan
authors.forename: Perumal
authors.initials: P
authors.lastname: Venkatachalam
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D001761:Bleomycin / Q000494:pharmacology* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D024201:Bystander Effect / Q000187:drug effects*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005260:Female; D042822:Genomic Instability / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006657:Histones / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; C468783:H2AX protein, human; D006657:Histones; D009363:Neoplasm Proteins; D001761:Bleomycin
keywords: Bleomycin; Bystander response; Cell cycle kinetics; Glioblastoma; H2AX; Micronucleus