# CELLULAR MECHANISMS OF HYPERTHERMIA DAMAGE

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 1990 · $195,591

## Abstract

The long term objective of the proposed research is to gain an
understanding of the cellular lesions induced by hyperthermia that
kill mammalian cells.  Knowledge of the cellular/molecular lesions
by which heat kills cells is important in developing clinical
protocols using heat alone and in combination with other
therapeutic modalities in the treatment of cancer.

This proposal focuses on three of the cell's structural systems as
potential targets of critical heat damage.  These structural
systems are:  1) the cytomatrix; 2) the nuclear envelope/lamina
complex; and 3) the nuclear matrix.  The major aim will be to test
the hypothesis that unrepaired heat-induced structural damage to
these systems will result in cell death. A comprehensive
quantitative morphological study of the effects of heat on these
three systems using synchronous CHO cells is proposed.  Cells will
be examined at varying times beginning immediately after treatment
to determine repairable and irreparable lesions.  The morphological
endpoints will be compared to cell survival.  The effects on
modifying survival on the morphological endpoints will be assessed
using heat sensitizers (local anesthetics, caffeine, low pH) and
thermally sensitive CHO mutants with altered morphology will be
used in the proposed experiments.

The morphological integrity of the various systems will be studied
using light microscopy (bright field, phase, and differential
interference contrast) fluorescence microscopy, time lapse
cinematography, and transmission electron microscopy.  Emphasis
will be placed on using synchronous cells, sequential extraction
of cells that produce well-defined fractions of both morphological
and biochemical use, and resinless section electron microscopy for
quantifying ultrastructural damage to the three systems.  Emphasis
will also be placed on the use of the premature chromosome
condensation technique as a functional assay of heat-placed on the
use of the premature chromosome condensation technique as a
functional assay of heat-induced alterations to the nuclear
matrix/chromatin complex and for studies of the nuclear
envelope/lamina system.  Results from this project should
demonstrate whether or not heat induces critical lesions to the
structural systems under study, with repair of the damage being a
pre-requisite for reproductive integrity.

## Key facts

- **NIH application ID:** 3176819
- **Project number:** 5R01CA038656-06
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **SAM.gov UEI:** R8JEVL4ULGB7
- **Principal Investigator:** RONALD Allen COSS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $195,591
- **Award type:** 5
- **Project period:** 1985-07-01 → 1993-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3176819

## Citation

> US National Institutes of Health, RePORTER application 3176819, CELLULAR MECHANISMS OF HYPERTHERMIA DAMAGE (5R01CA038656-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3176819. Licensed CC0.

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