Ultrasonic enhancement of cytotoxic effects of nitrogen mustard in mouse leukemia

Mouse leukemia L1210 is extensively used as a model for cancer chemotherapy drug screening. Animal median survival time (MST) is proportional to the log of the number of viable (capable of dividing) leukemic cells (LC) inoculated. Chemotherapeutic agents increase MST apparently by rendering a fraction of the LC incapable of dividing. LC obtained from DBA/2 mouse ascites fluid were placed in saline suspension in a Teflon/Saran chamber for 10 min at 22°–30°C. Healthy 18‐ to 22‐g BDF1 mice were then inoculated intraperitoneally with 105 LC from the chamber resulting in MST of 10.0 days (range 8.0–15.5/n = 36 animals). Exposing LC to continuous 1.9 MHz 10 W/cm2 (17 W/cm2 spacial peak) ultrasound (US) for 10 min did not alter MST. Addition of 0.5 μg/ml nitrogen mustard to the suspension without US increased MST to 10.5 (9.0–12.5/n = 21) and with US increased MST to 13 (10.5–14/n = 20). A 2.5 day MST increase is equivalent to 98% cell kill. Doubling nitrogen mustard concentration (1 μg/ml) without US increased ...