Reduction of erythropoietic toxicity to cytarabine by pentobarbital

The erythropoietic toxicity of cytarabine was reduced when mice were maintained in the anesthetized state by pentobarbital starting 1 hr before and lasting 1 hr after a series of doses of cytarabine given over a 4 hr period. Erythropoietic toxicity was determined by injecting 59Fe 48 or 72 hr after the last dose of cytarabine and measuring 59Fe in the circulating red blood cells 24 hr later (24 hr 59Fe uptake). Although pentobarbital alone had no effect on 24 hr 59Fe uptake either 48 or 72 hr after pentobarbital, the barbiturates reduced erythropoietic toxicity when cytarabine was given as 3 doses of 50 or 100 mg/kg every 2 hr and the effect was evaluated 48 hr after the last dose. Neither single nor multiple doses of cytarabine inhibited 59Fe uptake when 24 hr 59Fe uptake was measured 72 hr after cytarabine. However, if an initial dose of cytarabine (150 mg/kg) was given 12 hr prior to the multiple doses and 24 hr 59Fe up take was measured 72 hr after drug treatment, 59Fe uptake was inhibited, suggesting that the initial dose of cytarabine induced hemopoietic stem cells in the resting GO state to go into active cell cycle. Pentobarbital also protected against these latter effects of multiple doses of cytarabine. In contrast to the above, pentobarbital did not protect against the inhibitory effects of a single dose of cytarabine on 59Fe uptake. The above data show that pentobarbital protects against the cytotoxic effect of cytarabine on pronormoblasts and hemopoietic stem cells in cell cycle.