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 exponentially 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 (approximately 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.
Johnston
P J
PJ
School of Biological and Medical Sciences, University of St Andrews, Fife, U.K.
Bryant
P E
PE
D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D002460:Cell Line; D002875:Chromosomes / Q000187:drug effects* / Q000648:ultrastructure; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D013301:Streptolysins
D013301:Streptolysins; D001761:Bleomycin