Winner of the 1988 Lund Science Award: Hydralazine-induced enhancement of hyperthermic damage in a C3H mammary carcinomain vivo

Abstract

Prolonged oxygen deprivation of cells in vitro or in vivo increases the sensitivity of those cells to heat. Hydralazine is a peripheral vasodilator, currently used clinically as an antihypertensive agent, which has been reported to be able to reduce tumour blood flow and increase the degree of tumour hypoxia. We have investigated the potential of hydralazine to enhance the response of a C3H mammary carcinoma to local hyperthermia. The tumour was grown in the foot of mice and its response to treatment assayed by regrowth delay. Our results show that a single intravenous injection of hydralazine (5 mg/kg) significantly enhances the heat damage produced by heating for various times at either 41.5, 42.5, or 43.5°C. This effect was dependent on the time of starting to heat after hydralazine injection, with the greatest enhancement occurring when heat was given within 1 h following drug administration. However, the effect was independent of the hydralazine concentration, at doses above 2.5 mg/kg. Hydralazine also significantly decreased mean arterial blood pressure and the uptake of ⁸⁶RbCl into tumours. Our results suggest that the observed heat sensitization was primarily a consequence of an increase in tumour hypoxia, probably resulting from a decrease in tumour blood perfusion.