Increased in vitro toxicity to mouse bone marrow with 1,3-bis(2-chloroethyl)-1-nitrosourea and hyperthermia

Hyperthermia has been shown to increase the cytotoxic effect of certain cancer chemotherapeutic agents in vitro and in vivo. It is not known whether the combination of hyperthermia plus these chemotherapeutic drugs will also increase the toxicity of the drugs. This study was undertaken to evaluate the toxic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea combined with hyperthermia on normal mouse bone marrow in vitro. An increased effect of the combination was seen when the marrow was heated at 42 degrees in the presence of the drug for 15 min (p less than 0.025) and for 1 hr (p less than 0.005). Incubations for 2 hr produced a significant decrease of control growth, such that no increased effect of the combination of drug plus hyperthermia could be seen. In order for the increased effects to be seen, heating had to be done simultaneously in the presence of the drug. Clinicians using the combination of whole-body hyperthermia plus 1,3-bis(2-chloroethyl)-1-nitrosourea should be aware of possible increased marrow toxicity.