The toxicity of 1-[2-(diethylamino)ethyl]
reserpine (DL-152) has been measured for 4 transplantable mouse
tumors.
DL-152 was found to be toxic to cells of all the
tumor models tested (KHT
fibrosarcoma, RIF-1
fibrosarcoma, EMT-6
adenocarcinoma and
Lewis lung carcinoma) when the
drug was given by
intraperitoneal injection to the
tumor-bearing mouse and cell survival was measured by excision assay. For the KHT
tumor, hypoxic cells were found to be more sensitive to the
drug in vivo than were aerated cells, and a similar response to
hypoxia was observed in vitro, suggesting that sensitization occurred at the cellular level. Neither EMT-6 nor RIF-1
tumors showed increased sensitivity to the
drug when cells were exposed under hypoxic conditions in vivo or in vitro. However, when the response of aerated cells of the 3
tumors was compared, the relative sensitivities for
tumors exposed in vivo did not show the same ranking as the results of in vitro toxicity assays. This difference in in vitro and in vivo response in the different
tumor models did not appear to be related to pharmacokinetic factors since the maximum tissue concentration and the rate of clearance of the
drug were similar for all the
tumors studied.