NIEHS Initiatives

THE CELL MEMBRANE is a recognized site for radiation injury (Myers, 1970; Alper, 1971). Chemical agents known to interact with membrane components may therefore amplify cell killing when present during irradiation. Indeed membrane-active agents such as local anaesthetics, analgesics and tranquillizers have been shown to enhance radiation effects on cells (George et al., 1975; Shenoy et al., 1975). A commonly used tranquillizer, chlorpromazine HCI (CPZ), has shown great promise in increasing the radiation sensitivity of hypoxic bacterial and mammalian cells in vitro (Shenoy et al., 1975) as well as mouse solid tumours in vivo (George et al., 1980; Shenoy & Singh, 1980). This drug also showed preferential cytotoxicity to hypoxic bacterial cells (Shenoy & Singh, 1978) and a mouse fibrosarcoma in vivo (George et al., 1980). Since the plasma membrane is also the main organelle involved in heat-killing of cells (Har-Kedar & Bleehen, 1976) CPZ, by virtue of its membrane activity, might potentiate the therapeutic effect of hyperthermia. We have therefore investigated the effect of CPZ on the thermal sensitivity of two murine solid tumours in vivo. The tumours used in the present study were a sarcoma 180 (Si80) and a fibrosarcoma described elsewhere (Shenoy & Singh, 1980: George et al., 1980). Both were serially transplantable and grown s.c. on the ventral wall of the thorax of 8-week-old female Swiss mice weighing Accepte(d 19 October 1981