Effects of hyperthermia on binding, internalization, and degradation of epidermal growth factor

B. E. Magun, C. W. Fennie

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

125I-epidermal growth factor was used as a molecular probe to study the effects of hyperthermia and local anesthetics on cultured Rat-1 cells at 45°C for times up to 1 hr caused a continuous decrease in EGF binding. Scatchard analysis showed that the decreased binding resulted from a decrease in the affinity of the EGF receptors rather than from a decrease in receptor number. Whereas hyperthermia as high as 45°C for 30 min did not inhibit the process of receptor-mediated endocytosis of EGF, the degradation of internalized EGF was strongly inhibited at temperatures from 43 to 46°C. Exposure to 42°C had no effect on degradation. Because EGF degradation has been shown to occur in lysosomes, the authors compared the effects of heat to those caused by the local anesthetics procaine and lidocaine, which have been shown to prevent EGF degradation. The latter compounds, as well as other lysosomotropic amines, were similar to hypothermia in their ability to permit accumulation of internalized EGF by preventing degradation. Because procaine and lidocaine have been shown by other to potentiate the killing effects of hyperthermia on tumors and in cultured cells, they suggest that hyperthermia and the local anesthetics may act at the same cellular site. By inhibiting the action of lysosomes, hyperthermia and local anesthetics may permit potentially toxic materials to enter the cell by endocytosis, where they would accumulate and induce lethal damage.

Original languageEnglish (US)
Pages (from-to)133-146
Number of pages14
JournalRadiation Research
Volume86
Issue number1
Publication statusPublished - 1981
Externally publishedYes

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biophysics
  • Radiology Nuclear Medicine and imaging
  • Radiation

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