Effect of reserpine (NSC 59272) induced hypothermia on lifespan in mouse L1210 leukemia

In order to employ in vivo model systems for the chemotherapeutic evaluation of agents that also happen to produce hypothermia in test animals, it is necessary that the effect of hypothermia itself on tumor growth or survival parameters be considered. Reserpine was used to produce a stable hypothermia in BDF₁ mice bearing L1210 ascites leukemia. Mice were maintained at ten different ambient temperatures ranging from 22 to 33°C and the percent increase in median and mean lifespan with respect to controls similarly maintained was determined. Increases in median and mean lifespan of 40%-50% were obtained by means of reserpine induced hypothermia. Reserpine itself did not increase survival time when hypothermia was prevented by keeping the treated mice at elevated ambient temperature, under conditions in which reserpine alone was nontoxic. Hypothermia was a major contributing factor to the previously observed antileukemic effects of reserpine in the L1210 system and very likely in other murine tumor systems. Thus, any potential chemotherapeutic agent that also happens to produce hypothermia could give a very substantial positive result due to hypothermia alone. By use of an empirical relationship presented between survival parameters and either average temperature or a hypothermia parameter defined as temperature time below controls, it is now possible to make a firm quantitative correction for effects due to hypothermia alone. A possible approach to detecting and monitoring drug induced hypothermia in mass screening systems is suggested.