Bleomycin: mammalian cell lethality and cellular basis of optimal schedule

Experiments on the dose- and time-dependent changes in the survival of Ehrlich ascites tumor cells exposed to bleomycin were done to determine a useful regimen for the effective inactivation of the tumor cells. The experimental results on time-dependent changes in survival of bleomycin-treated cells indicated that two phenomena were involved in the survival increase observed after single bleomycin treatment: 1) The bleomycin-treated cells were resistant to the second injection when the interval between the two successive doses was within 2 hours (induced resistance), and 2) the survival was increased as a function of time when the interval between treatments was prolonged (repair of potentially lethal damage). The effect of the fractionated treatments was then investigated for the regimen that minimized the induced resistance and repair of potentially lethal damage. The results indicated that administration of a lower dose of bleomycin at shorter intervals was more effective than other fractionation schedules, and, on the basis of the same dose rate, the continuous infusion regimen was more effective than fractionation regimens for the sterilization of Ehrlich ascites tumor cells.