Modification of bleomycin-induced chromosome aberrations by hyperthermia and under energy depleting conditions in...

Synergistic effects of bleomycin (BLM) and hyperthermia were studied in human peripheral lymphocytes (HPL). The frequencies of breaks produced by BLM were dependent on dose, incubation temperature, and treatment time. Heat alone did not induce chromosome aberrations. Synergistic effects of heat and BLM occurred at 43 degrees C, either when hyperthermia was for 60 min following treatment with BLM or when hyperthermia was for 30 min simultaneously with BLM treatment. At incubation temperatures below 43 degrees C as many dicentric chromosomes as chromosome breaks were found, but about twice as many dicentric chromosomes as chromosome breaks were found when cells were treated with BLM at 43 degrees C for 60 min. In all experiments with BLM chromosomal anomalies were overdispersed. Comparison with unstimulated HPL, heated after X-irradiation, suggested that heat inhibits repair of BLM-induced lesions to a smaller extent than X-ray-induced lesions. Experiments with sodium azide and 2-deoxyglucose led to the conclusion that cellular uptake of BLM is partly energy-dependent. Additionally, an energy-independent uptake of BLM, which could not be blocked by inhibitors, was apparent.