CHROMOSOME-DAMAGE INDUCED BY NANOMOLAR CONCENTRATIONS OF BLEOMYCIN IN PORATED MAMMALIAN-CELLS

We have examined chromosome damage caused by a wide range of bleomycin (BLM) concentrations in Chinese hamster ovary (CHO-K1) cells reversibly porated by the bacterial cytotoxin streptolysin-O (SLO). Chromosome damage was measured using the micronucleus cytokinesis block technique (employing cytochalasin-B). Treatment of exponentiaily growing cells with 0.045 IU/mL SLO for 5 min resulted in up to a thousand-fold and a million-fold increase in biological effectiveness, compared to treatment in the absence of SLO for 24 hr and 5 min, respectively. Increases in micronuclei of 4-5 times background level were observed after only 5 min exposure to the drug in the presence of SLO at doses as low as 100 pg/mL (almost-equal-to 70 pmol/L). These results indicate that the use of SLO may facilitate the treatment of cells with BLM for periods of time resembling acute exposure to ionizing radiations.