Modification of the balance between damage and repair of bleomycin-induced DNA-strand breakage by hyperthermia.
It is well recognized that hyperthermia can greatly enhance the cytotoxic effect of bleomycin. It has been suggested that the mechanism of hyperthermic potentiation of bleomycin toxicity involves the inhibition of DNA repair function. We have investigated how hyperthermia can modify the repair capacity of bleomycin treated cells by monitoring the induction of DNA damage and repair, using two essentially different techniques (DNA unwinding assay and nucleoid sedimentation assay). We have also investigated whether the enhancement of DNA-damaging potential of bleomycin was related to the availability of new sites within chromatin for drug attack. We have found that heat treatment (even for non-toxic exposures of 30 min at 44 degrees C) restricts the access of active drug to DNA, probably by the increase in nuclear protein content. The results obtained show that the increase in drug-induced DNA damage in heat-treated cells probably represents an underestimation of the predominant effect of hyperthermia on reducing cellular DNA repair capacity.
D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D002478:Cells, Cultured; D002843:Chromatin / Q000187:drug effects; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D006979:Hyperthermia, Induced; D007700:Kinetics
D002843:Chromatin; D001761:Bleomycin