Ferrous iron-mediated enhancement of DNA damage and recovery potential in bleomycin-treated human cells.

Damage to cellular DNA is generally considered to be responsible for the antitumour activity of bleomycin. In view of the ferrous oxidase properties of the drug, ferrous iron supply has been manipulated to enhance bleomycin-induced DNA cleavage so that the relationship between the initial yield of DNA damage and cell survival could be explored in a human transformed fibroblast cell line. Bleomycin-induced DNA strand breaks were quantitated by either alkaline denaturation or neutral nucleoid sedimentation techniques. Exogenously supplied ferrous iron greatly enhanced the initial frequency of frank DNA strand breaks and alkali-labile lesions without affecting gross cellular repair capacity. Despite the increased levels of DNA damage, the presence of ferrous iron (greater than 3 microM) significantly increased (factor up to 2-fold; P less than 0.05) the survival capacity of drug-treated cells. It is concluded that the induction of DNA damage which can promote cellular recovery may contribute to the variability of the in vivo efficacy of bleomycin.