# EFFECTS OF ANTIMETABOLITES ON RNA METABOLISM

> **NIH NIH R01** · ROSWELL PARK CANCER INSTITUTE · 1992 · $79,038

## Abstract

The purpose of this application is to extend previous studies of the
effects of 5-fluorouracil (FUra) on RNA metabolism in an effort to better
understand the RNA mediated effects of FUra cytotoxicity.  This study will
focus on two FUra induced aberrations of mRNA metabolism, pre-mRNA splicing
and mRNA half life.  It is specifically proposed that the following be
accomplished:

1.  Apply the polymerase chain reaction to quantitate steady state levels
of dihydrofolate reductase (DHFR) RNA splicing substrates as well as
splicing intermediates in the pre-mRNA processing pathway, in FUra treated
and control cells.  Extend this assay to non-gene amplified cells so that
it may eventually be applied in vivo.

2.  Measure the half life of 3.5 kb DHFR mRNA in cells grown in the
presence or absence of FUra.  Assess whether an increased half-life after
cell growth in medium containing FUra is an explanation for the previously
observed increase in this specific DHFR mRNA.  Identify the 3' noncoding
element(s) present in 3.5 kb DHFR mRNA which appear to mediate this effect
of FUra on half-life deletion mapping and DNA transfection.

3.  Study the effect of FUra pretreatment on methotrexate cytotoxicity in
cells expressing mRNAs with altered 3' noncoding regions to correlate
alterations in mRNA half life with DHFR drug responsiveness.

## Key facts

- **NIH application ID:** 3172016
- **Project number:** 5R01CA034301-09
- **Recipient organization:** ROSWELL PARK CANCER INSTITUTE
- **Principal Investigator:** BRUCE JEFFREY DOLNICK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $79,038
- **Award type:** 5
- **Project period:** 1988-05-01 → 1993-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172016

## Citation

> US National Institutes of Health, RePORTER application 3172016, EFFECTS OF ANTIMETABOLITES ON RNA METABOLISM (5R01CA034301-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172016. Licensed CC0.

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