# HYPERTHERMIA AND INTRACELLULAR PH AND CA2

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 1988 · $52,346

## Abstract

The overall objective is to address the questions of whether a diminished
capacity to regulate intracellular pH (pHi) and free cytoplasmic Ca2+
(pCai) at temperatures achievable during local hyperthermia can be
correlated with thermal cell death and whether modification of pHi and pCai
by specific drugs and other agents can sensitize cells to heat.  Results
obtained will relate directly to mechanisms by which heat kills tumor cells
and the development of thermotolerance and as such has implications for
enhancement of clinical local hyperthermia.

Regulation of pHi and pCai by V79 fibroblasts in log and plateau phase
growth will be examined before, during and after heat treatments (37-45C)
and with thermotolerant cells as a function of extracellular pH (pHe) with
and without intracellular acid loading.  Mitochondrial membrane potential,
lysosomal pH and cytoplasmic pHi and pCai will be determined with
fluorescent probes and either a conventional fluorescence spectrophotometer
or a fluorescence microscope coupled to an intensified photodiode array to
allow for measurements at the single cell level.  For short term pHi
regulation, cellular buffer capacity and mitochondrial function in situ
will be assessed as a function of temperature.  For long term pHi
regulation, the capacities of Cl-:HCO3-, Na-dependent Cl-:HCO3- and Na+:H+
exchange processes are judged from effects of anion transport inhibitors
(disulfonic stilbenes) and inhibitors of Na+ transport (furosemide and
amiloride).  Evidence for a H+ pump will also be obtained.  Regulation of
pCai will be examined in terms of mitochondrial function and
interrelationships with pHi.  Correlations of cell survival with ability of
cells to regulate pHi and pCai will be based on the reversibilities of
these processes after heat treatment, examination of thermotolerant cells
and the effects of the above inhibitors on cell survival.  The development
of photometric fluorescence microscopy to single cell analysis and its
application to hyperthermia studies may allow for the biochemical
characterization of thermotolerant cells and cells doomed to die after heat
treatment.

## Key facts

- **NIH application ID:** 3176765
- **Project number:** 7R01CA038639-05
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **SAM.gov UEI:** MLQFL4JSSAA9
- **Principal Investigator:** ROSS B MIKKELSEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $52,346
- **Award type:** 7
- **Project period:** 1985-01-01 → 1989-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3176765

## Citation

> US National Institutes of Health, RePORTER application 3176765, HYPERTHERMIA AND INTRACELLULAR PH AND CA2 (7R01CA038639-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3176765. Licensed CC0.

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