# MECHANISM OF RADIOPROTECTION BY AMINOTHIOLS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 1993 · $328,225

## Abstract

DESCRIPTION (Investigator's Abstract):  The long term goal of this research
is to elaborate how aminothiols and their derivatives function in
protecting cells against radiation damage.  The methodology used includes
model system studies in which damage is assessed as single and double
strand breaks in DNA.  A broader assessment of damage is obtained by
measuring the viability of a DNA plasmid carrying antibiotic resistance
genes using a suitable E. coli host.  DNA model systems used include pBR322
plasmid DNA, SV40 plasmid DNA, and SV40 minichromosomes.  Radioprotection
by aminothiols in cells is studied using cultured Chinese Hamster lung
fibroblasts (V79-171 cells) with cell viability as the indicator of lethal
cell damage.  DNA damage in cells is assessed using neutral and alkaline
elution assays to measure strand break damage.  Monitoring of thiol levels
is important because cellular levels vary with incubation conditions and
with thiol structure, and even with DNA alone thiols are easily converted
to disulfides by radiation.  In all of these studies thiol and disulfide
levels will be monitored by fluorescent labeling and HPLC separation
methods developed in this laboratory.  Specific aims for this grant period
are:  (1) to determine if water-octanol partion coefficients for
aminothiols allow prediction of uptake by passive diffusion in cells; (2)
to establish if polyamine transport systems contribute to uptake of WR1065
by cells; (3) to determine the kinetic parameters which characterize
protection of V79 cells by endogenous thiols and aminothiol radioprotectors
under physiologic oxygen tension; (4) to determine if thiols protect pBR322
against strand break damage and loss of transforming ability in the same
manner; (5) to obtain the parameters which characterize aminothiol
protection of pBR322 under low oxygen tension at room temperature; (6) to
develop a DNA model which reflects the thiol nonprotectable damage (TNPD)
seen with cells; (7) to evaluate the relative contribution of thiol and
thiolate forms in radioprotection of plasmid DNA; (8) to evaluate the
importance of steric factors in protection of DNA by thiols; (9) to
ascertain how chemical repair of oxygen-dependent damage by thiols in E.
coli varies with net charge on the thiol.  The results improve our ability
to predict cell radioprotection from results of DNA model studies, will
provide insight concerning optimal administration of the aminothiol drug
WR2721 which is currently undergoing clinical trials, and will assist the
design of improved radioprotective compounds.

## Key facts

- **NIH application ID:** 3178727
- **Project number:** 2R01CA039582-09
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **SAM.gov UEI:** UYTTZT6G9DT1
- **Principal Investigator:** ROBERT C FAHEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $328,225
- **Award type:** 2
- **Project period:** 1985-04-01 → 1996-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178727

## Citation

> US National Institutes of Health, RePORTER application 3178727, MECHANISM OF RADIOPROTECTION BY AMINOTHIOLS (2R01CA039582-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178727. Licensed CC0.

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