# BIOCHEMICAL RESPONSES OF HYPOXIC CELLS TO CHEMOTHERAPY

> **NIH NIH R01** · GEORGE WASHINGTON UNIVERSITY · 1988 · $71,555

## Abstract

Significant advances toward the cure of human cancer have been
achieved in rapidly growing cancers such as childhoold tumors and
Hodgkin's disease.  The relatively slow growing solid tumors (e.g.
lung, colon and breast carcinomas) have responded poorly to
existing chemotherapeutic agents.  By understanding the
biological responses of the subpopulations of solid tumors to
chemotherapy, effective treatment regiments may be designed to
attack each population.  One important biological subpopulation
of neoplastic cells present in solid tumors is the hypoxic tumor
cell.  Data from our laboratroy indicate that neoplastic cells in
hypoxic tumor cell.  Data from our laboratory indicate that
neoplastic cells in hypoxic environments cannot maintain the
integrity of their own DNA, have difficulty in repairing at least
two kinds of DNA damage, have lower levels of glutathione, and
may be more sensitive to the mutagenic effects of some
chemicals when these hypoxic cells are compared with normally
aerated cells.  The overall goal of this research is to understand
the biological responses of neoplastic cells to conditions of low
oxygen and to understand the biochemical and pharmacological
parameters which influence the responses of these hypoxic tumor
cells to cytotoxic drug therapy.  To accomplish this goal, we
intend to determine the ability of hypoxic cells to accumulate and
repair DNA damage during severe and moderate hypoxia; to
determine the ability of hypoxic tumor cells to repair mitomycin
C induced DNA damage under continued hypoxic exposure or
under reoxygenated conditions and to correlate the repair of
damage with altered cell survival; to determine the ability of
hypoxic tumor cells to restore glutathione levels after depletion
by hypoxia, diethylmaleate or by buthionine-S, R-sulfoximine; to
assess the ability of hypoxic cells to maintain adequate levels of
ATP; and to determine the susceptibility of hypoxic cells to
mutation as a measure of their potential to become resistant to
chemotherapeutic agents.  Colony formation assays, alkaline
elution techniques, high performance liquid chromatography, and
mutation assays wil be used to assess cell survival, DNA damage,
adenine nucleotide levels, and mutation.

## Key facts

- **NIH application ID:** 3174620
- **Project number:** 5R01CA036946-05
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **SAM.gov UEI:** ECR5E2LU5BL6
- **Principal Investigator:** KATHERINE A. KENNEDY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $71,555
- **Award type:** 5
- **Project period:** 1984-04-01 → 1990-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174620

## Citation

> US National Institutes of Health, RePORTER application 3174620, BIOCHEMICAL RESPONSES OF HYPOXIC CELLS TO CHEMOTHERAPY (5R01CA036946-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174620. Licensed CC0.

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