Bystander Effects in Repair-Deficient Cell Lines

One of the current hypotheses concerning the role of bystander effects in biological systems is that they are protective because they terminate division in cells with collateral or possibly pre-existing DNA damage that is not properly repaired. Following the logic of this hypothesis led us to consider that cell lines that are repair deficient should have larger than usual bystander effects. To test this, several different "repair- deficient" cell lines were used for bystander experiments. Response was monitored by determining the cloning efficiency or, in the case of non-adherent cell lines, the cell number. The results show that the repair-deficient human cell lines and surviving progeny produced moderate to severe bystander- induced death effects in either autologous cells or a reporter cell line. Normal "repair-proficient" lines, which were matched as far as possible, have very much less severe or absent bystander-inducible effects on cloning efficiency. Cells of hamster cell lines derived from CHO-K1 cells did not produce similar severe effects. The results suggest that repair- deficient human cell lines, irrespective of the actual repair defect, may respond to the occurrence of DNA damage in the population by removing large numbers of cells from the proliferating pool.