Hyperthermia and cytotoxic drugs. Possible use of lanthanum as a potentiator of hyperthermia.

Abstract

Recent studies indicate that differences in membrane fluidity may account for differences of thermal sensitivity. This possibility was studied by using lanthanum, a trivalent cation which is known to displace calcium in a number of biological systems, to modify the structural framework of cell membranes and consequently their biological properties. With Ehrlich ascites cells trypan blue exclusion uptake of 86Rb, 42K and 45Ca, indicate an increase of plasma cell permeability by La3+. The reduction of 86Rb and 42K uptake by tumour cells with La3+ appears to be independent of temperature. The increase of 45Ca2+ influx in the presence of lanthanum plus hyperthermia seems related to an important loss of cell viability. The enhancement of hyperthermia lethality by concentrations of lanthanum over 0.5 mM after 2 h at 44 degrees C has been demonstrated using HeLa S3 cells using a standard cloning technique. In vivo experiments have been performed on C3H mice bearing rhabdomyosarcoma using ultrasound heating at 44-46 degrees C. The results show a remarkable inhibition of tumour growth and a significant increase of the survival time after only one hyperthermia session of 30 min combined with one intratumoural injection of 1 mM lanthanum chloride.