Arrhenius analysis of the heat response in vivo and in vitro of human melanoma xenografts

Abstract

The response to heat treatment in vivo (40.5–44.0°C) and in vitro (40.5–45.5°C) of five human melanoma xenografts was studied. Specific growth delay was used as a measure of response after treatment in vivo. Colony-forming ability was assayed in soft agar after treatment in vitro. Doseresponse curves were established and subjected to Arrhenius analysis. The Arrhenius curves were found to have an inflection point at 42.0–43.0°C in vivo and 41.5–42.5°C in vitro. The activation energies were in the ranges 426–771 kJ/mol in vivo and 676–739 kJ/mol in vitro above the inflection point and 774–1661 kJ/mol in vivo and 1118–2190 kJ/mol in vitro below the inflection point. Above the inflection point the activation energies in vivo and in vitro were not significantly different for any of the melanomas, and furthermore were similar to those reported for rodent tumours, normal tissues and cells in culture in the same temperature range. Below the inflection point on the other hand the activation energies were lower in vivo than in vitro. This difference was probably a consequence of differences in the physiological conditions in vivo and in vitro. The activation energies in vitro in this temperature range were comparable to those reported for normal tissues and cells in culture.

Key Words:

• heat cytotoxicity
• activation energies
• tumour physiology
• melanoma xenografts