# CELLULAR THERMOSTABILITY AND THERMOTOLERANCE

> **NIH NIH R01** · UNIVERSITY OF WATERLOO · 1988 · $17,000

## Abstract

Hyperthermia has considerable promise as a means of cancer therapy, at
least for tumors refractory to other means of treatment but situated such
that they can be effectively heated.  It should be particularly effective
in combination with radiation and certain chemotherapeutic agents.  The
molecular effects of hyperthermia are not well understood; in particular
the target (if there is a single one) of hyperthermia and the molecular
basis of thermotolerance are not known.  The specific aims of this proposal
are to determine if the plasma membrane, mitochondria, nuclei, or the
cytosol of cells become more thermostable in thermotolerant cells.
Thermostability will be assayed by measuring the temperature at which
protein denaturation occurs in the organelles listed above and in whole CHL
V79 cells using ultra-high sensitivity differential scanning calorimetry
(DSC) and spin labeling.  This will give information about whether the
state of cellular thermotolerance is due to increased thermostability of
cellular organelles and which organelles might be the direct targets of
hyperthermia.  Each of the isolated organelles investigated will be
analyzed for the presence of het shock proteins (HSP's) by SDS-PAGE
autoradiography.  Thus, it will be determined whether HSP's may be directly
responsible for thermotolerance by increasing the thermostability of
cellular organelles by binding to them.  The direct effects of previously
identified hyperthermic sensitizers and protectors on the thermostability
of the cellular organelles listed above will also be determined by DSC.

A second aspect of this proposal deals with measuring protein denaturation
in whole V79 cells at 40-45 degrees C by ultra-high sensitivity DSC and
relating the degree of protein denaturation to cell survival determined by
colony assay.  This will give a rapid (about one hour), relatively simple
means of both assaying the hyperthermic sensitivity of cells and the degree
of damage induced by a prior heat treatment.  This will be extended to the
development of a method for assaying the damage produced by a heat
treatment in EMT6 tumors previously grown in BALB/c mice.  If this is
successful, a method will have been developed for determining the
effectiveness of a hyperthermic treatment immediately after, or possibly
during, treatment.

## Key facts

- **NIH application ID:** 3179960
- **Project number:** 3R01CA040251-03S1
- **Recipient organization:** UNIVERSITY OF WATERLOO
- **SAM.gov UEI:** RHJRA5J1A2B5
- **Principal Investigator:** JAMES R. LEPOCK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $17,000
- **Award type:** 3
- **Project period:** 1985-08-01 → 1988-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179960

## Citation

> US National Institutes of Health, RePORTER application 3179960, CELLULAR THERMOSTABILITY AND THERMOTOLERANCE (3R01CA040251-03S1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179960. Licensed CC0.

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