# THERMOTOLERANCE, PROTEIN SYNTHESIS, AND STEPDOWN HEATING

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 1987 · $119,568

## Abstract

Understanding thermotolerance is one of the major challenges of biology.
Thermotolerance can affect many cellular responses to subsequent
hyperthermia by factors of up to 10,000.  The impact of thermotolerance on
the clinical response to hyperthermia is only just beginning to be
appreciated.  Taking advantage of thermotolerance, or avoiding it could
significantly alter the way hyperthermia is used in tumor therapy.  This
study is designed to test the hypothesis that protein synthesis (perhaps
heat shock proteins) is required for thermotolerance development in
mammalian cells, that the rate of protein synthesis at different
temperatures influences the rate of thermotolerance development resulting
in the "break" in the Arrhenius plot at approximately 43 degrees, that
inhibition of protein synthesis by cycloheximide (CHM) will inhibit
thermotolerance development, and that reduced protein synthesis at high
temperature-low temperature combinations leads to the phenomenon of
"stepdown" heating.  The hypothesis will be tested in both G1 and S-phase
cells so that cell cycle specific differences in hyperthermia response will
not affect the results.  This study will use Chinese hamster ovarian
carcinoma (OvCa) cells and at times Chinese hamster ovary (CHO) fibroblasts
in culture.  Considerable preliminary information from this laboratory
exists on the temperature kinetics of thermotolerance development, on the
effects of 45 degrees-hyperthermia on macromolecular synthesis, and on
stepdown heating in asynchronous populations.  The reason for using two
cell lines is that the OvCa cell is much more efficient at developing
thermotolerance than CHO.  The endpoints are plating efficiency, cell
attachment, rate of cell division, protein synthesis, and DNA synthesis.
Synchronous populations are obtained by mitotic selection.  The effects of
low pH, nutritional deprivation, and the addition of glycerol or lidocaine
on the relationship between thermotolerance, protein synthesis and stepdown
heating will be investigated.  The results of this study will further
define the role of protein synthesis in thermotolerance induction,
development and decay; will suggest ways whereby one might differentially
enhance or prevent thermotolerance development; will show the cell cycle
dependency of thermotolerance development; and will provide insight on how
stepdown heating may be used in regional or wholebody hyperthermia.  All
four results have the potential for significantly influencing the choice of
sequence of different temperatures, fractionation intervals, and the
addition of sensitizing or protective agents to improve therapeutic results.

## Key facts

- **NIH application ID:** 3178516
- **Project number:** 5R01CA039487-03
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **SAM.gov UEI:** R8JEVL4ULGB7
- **Principal Investigator:** DENNIS B. LEEPER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $119,568
- **Award type:** 5
- **Project period:** 1985-09-01 → 1988-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178516

## Citation

> US National Institutes of Health, RePORTER application 3178516, THERMOTOLERANCE, PROTEIN SYNTHESIS, AND STEPDOWN HEATING (5R01CA039487-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178516. Licensed CC0.

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