# MECHANISM OF CYTOTOXICITY OF DEOXYADENOSINE AND ANALOGS

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 1987 · $121,860

## Abstract

The biochemical mechanisms by which deoxyadenosine (in the prsence of an
adenosine deaminase inhibitor), 2-chlorodeoxyadenosine and
2-bromodeoxyadenosine exert their cytotoxic effects on cells will be
further investigated and compared.  These nucleosides are markedly
cytotoxic to human T-lymphoblastoid, B-lymphoblastoid and myeloid cell
lines in cutlure and produc therapeutic responses against murine tumors and
against human hemaologic malignancies.

One part of the project will be aimed at determining whether inhibition of
ribonucleoside diphosphate reductase by tripyhospahtes of the nucleosides
is the main mechanism of cytotoxicity.  Some of these experiments will
involved work with intact cells, and for this purpose the human
T-lymphoblastoid cell line CCRF-CEM will be used.  Other studies will
employ partially purified reductase from L1210 cells and highly purified
reductase from calf thymus.

In the second part of the project evidence will be obtained as to whether
inhibition of DNA synthesis by these necleosides involves another
signifiicant mechanism.  Particular attention will be given to the
possibility that DNA polymerase Alpha is inhibited, or that incorporation
of analogue into DNA inhibits chain elongation.  Purified DNA polymerase
Alpha will be used for these experiments.

The use of cells selected for resistance to the analogues will also be used
in both parts of the project.

## Key facts

- **NIH application ID:** 3178065
- **Project number:** 5R01CA039242-02
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **SAM.gov UEI:** JL4JHE9SDRR3
- **Principal Investigator:** RAYMOND L BLAKLEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $121,860
- **Award type:** 5
- **Project period:** 1986-02-01 → 1989-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178065

## Citation

> US National Institutes of Health, RePORTER application 3178065, MECHANISM OF CYTOTOXICITY OF DEOXYADENOSINE AND ANALOGS (5R01CA039242-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178065. Licensed CC0.

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