Compartmental stress responses correlate with cell survival in bystander effects induced by the DNA damage agent, bleomycin
Abstract
Physical or chemical stress applied to a cell system trigger a signal cascade that is transmitted to the neighboring cell population in a process known as bystander effect. Despite its wide occurrence in biological systems this phenomenon is mainly documented in cancer treatments. Thus understanding whether the bystander effect acts as an adaptive priming element for the neighboring cells or a sensitization factor is critical in designing treatment strategies. Here we characterize the bystander effects induced by bleomycin, a DNA-damaging agent, and compartmental stress responses associated with this phenomenon. Mouse fibroblasts were treated with increasing concentrations of bleomycin and assessed for DNA damage, cell death and induction of compartmental stress response (endoplasmic reticulum, mitochondrial and cytoplasmic stress). Preconditioned media were used to analyze bystander damage using the same end-points. Bleomycin induced bystander response was reflected primarily in increased DNA damage. This was dependent on the concentration of bleomycin and time of media conditioning. Interestingly, we found that ROS but not NO are involved in the transmission of the bystander effect. Consistent transcriptional down-regulation ...Continue Reading
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