The bystander effect: is reactive oxygen species the driver?

The paper reviews selected examples of the bystander effect, such as clonogenic survival decrease, chromosomal aberrations and mutations. The similarities and differences between the biological effects in directly targeted and bystander cells are briefly discussed. Also reviewed are the experimental data which support the role of reactive oxygen species (ROS), especially *O2-, as mediators of the bystander effect. Endogenously generated ROS, due to activation of NAD(P)H oxidases, play a key role in the induction of DNA damage in bystander cells. All the observed effects in bystander cells, such as alterations in gene expression patterns, chromosomal aberrations, sister chromatid exchanges, mutations, genome instability, and neoplastic transformation are the consequence of DNA damage.