# ARABINONUCLEOSIDE ACTIVATION IN LEUKEMIA CELLS

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 1987 · $108,884

## Abstract

The long range goal of this program is to improve the therapy of human
cancer with arabinonucleoside analogs.  This project is concerned with the
mechanism responsible for the selectivity of established and new
arabinonucleosides related to cytosine, adenine and guanine in murine
leukemia and human lumphoid model systems.  The following specific aims
will be sought:  Further aspects of the cytotoxic mechanism of newly
synthesized purine and pyrimidine deaminase-resistant 2'-0-nitronucleosides
termed nitrara-A and nitrara-C of arabinosyl-adenine and -cytosine,
respectively in human lymphoblastoid lines; use radiolabeled nitrara-C and
high pressure liquid chromatography to determine its metabolic fate in
plasma and activation (phosphorylation and incorporation into nucleic
acids) in murine leukemia and in human lymphoblastoid lines, including
those of T and B origin, with demonstrated differential sensitivity to the
drug; Evaluate in collaborative studies with colleagues from this
institution and elsewhere the antitumor and antiviral effects of the new
nitrate nucleosides and purine nucleoside phosphorylase-resistant
9-Beta-D-arabinosylguanine in animal model systems; purify and characterize
the nucleotidase enzymes in human lymphoid tissues for degradation of
active arabinonucleotides and deoxynucleotides; specific antibodies to
nucleotidases will be obtained to aid in the identification of the
enzyme(s) responsible in human lymphoblastoid of T and B origin (wild type
and mutants) for the catabolism of the arabinonucleotide analogs.
Nucleotidase activity and analog nucleotide retention will be examined in
sensitive and resistant cell lines to further define the relationship of
these two to arabinonucleoside metabolism and selectivity.

## Key facts

- **NIH application ID:** 3170926
- **Project number:** 5R01CA033017-06
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **SAM.gov UEI:** JL4JHE9SDRR3
- **Principal Investigator:** ARNOLD FRIDLAND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $108,884
- **Award type:** 5
- **Project period:** 1982-07-01 → 1988-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170926

## Citation

> US National Institutes of Health, RePORTER application 3170926, ARABINONUCLEOSIDE ACTIVATION IN LEUKEMIA CELLS (5R01CA033017-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170926. Licensed CC0.

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