REPAIR OF MITOCHONDRIAL-DNA DAMAGE-INDUCED BY BLEOMYCIN IN HUMAN-CELLS

Damage to mitochondrial DNA (mtDNA) has recently been associated with a variety of human diseases including cancer, diabetes mellitus, and aging. The mechanisms by which the mitochondria respond to DNA damage are of prime importance in understanding hew damage can persist and cause disease. Here we demonstrate the repair of mitochondrial DNA damage induced by the naturally occurring, radiomimetic drug bleomycin. WI-38 cells were first permeabilized using 20 mu g/ml lysophosphatidylcholine in order to increase the intracellular concentration of bleomycin. Dose response studies with the permeabilized cells showed that a concentration of 5 mu g/ml bleomycin given for 30 min caused sufficient DNA damage for repair studies. Following treatment with this concentration of bleomycin, repair of mtDNA damage was found to be about 80% by 2 h. However, after 4 h no additional repair was observed. The results indicate that there is an efficient DNA repair system in human mitochondria for some types of damage caused by bleomycin. However, there is a component of damage caused by this agent that either is not repaired or is removed at a much slower rate.