# CYTOTOXIC BASE PROPANOLS AND THE ACTION OF BLEOMYCIN

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 1988 · $119,039

## Abstract

The objective of this research is to define a molecular basis for the
cytotoxicity of bleamycin.  Several lines of evidence suggest that DNA
strand scission alone may not account for the cytotoxic effects of this
important antitumor agent.  An important clue has recently been provided by
the identification of several nucleoside base N-propenals produced by the
action of bleamycin on DNA.  These unsaturated aldehydes are highly
cytotoxic to tumor cells in culture and inhibit DNA synthesis.

The proposed research tests a novel hypothesis that base propenals produced
by the action of bleamycin on nuclear DNA inhibit critical cellular
processes, thereby accounting for the cytostatic and cytotoxic properties
of this drug.  Additional experiments have been designed to define the
molecular basis by which bleamycin produces single and double strand breaks
in DNA, to explore chemical mechanism(s) responsible for DNA degradation,
and to characterize adducts formed between base propenals and DNA.

Cytotoxicity reflects the chemotherapeutic potential of bleamycin and
underlies its principal side effect, pulmonary fibrosis.  The studies
proposed are directly relevant to cancer chemotherapy and have implications
for the development of new analogs of bleamycin.  This research should also
help to illuminate radical mechanisms involved in degradation of DNA by
other drugs, chemicals, and gamma-irradiation.

## Key facts

- **NIH application ID:** 3178950
- **Project number:** 5R01CA039663-03
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **SAM.gov UEI:** M746VC6XMNH9
- **Principal Investigator:** Arthur Patrick Grollman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $119,039
- **Award type:** 5
- **Project period:** 1985-09-30 → 1989-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178950

## Citation

> US National Institutes of Health, RePORTER application 3178950, CYTOTOXIC BASE PROPANOLS AND THE ACTION OF BLEOMYCIN (5R01CA039663-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178950. Licensed CC0.

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