# RADIOBIOLOGY OF RAT AND HUMAN HEPATOCYTES

> **NIH NIH R01** · DUKE UNIVERSITY · 1987 · $117,224

## Abstract

Reproductive survival studies demonstrate that parenchymal hepatocytes are
radioresistant (Do = 270 rad) and are significantly protected in vivo with
WR-2721, a thiophosphate derivative of cysteamine.  The overall objective
of this project is to elucidate the mechanism(s) for hepatocyte's enhanced
intrinsic resistance to ionizing radiation, and to explain the enigma that
though hepatocytes are radioresistant, the liver in situ is sensitive to
radiation damage.  Specifically, we will determine the importance of an
endogenous non-protein thiol (glutathione) and exogenously administered
WR-2721 in radioprotecting both rat and human hepatocytes.  The magnitude
of radiation damage before and after either the addition of WR-2721 or the
intracellular depletion of GSH (diethyl maleate or
buthionine-S,R-sulfoximine) will be estimated at the cellular level (ie,
reproductive survival) and at the molecular level (ie, DNA single strand
breaks).  The hepatocyte transplantation assay system which we
characterized will be used to estimate liver cell survival and DNA single
strand breaks will be determined with the alkaline elution technique.  The
ability of irradiated rat and human hepatocytes to repair enzymatically DNA
single strand breaks will also be compared with the efficacy of this repair
system in fibroblasts and hepatoma cells.  A rat model to investigate the
etiology of chronic radiation hepatitis will be developed to determine the
degree to which WR-2721 protects the liver in situ from chronic disease.
Additionally, the importance of parenchymal cell depletion in the
development of radiation hepatitis will be investigated by prophylactically
reseeding the irradiated liver with reproductively viable isolated
hepatocytes.  The experiments proposed in this application will enable us
to determine the role which non-protein thiols play in the protection of
both rat and human paranchymal hepatocytes.  Not only will these studies
delineate the mechanism of radioprotection; the interspecies comparisons
between rat and human liver cells will assist in the safe clinical
utilization of WR-2721 as a hepato-radioprotective agent and GSH depleting
agents for enhancing the effectiveness of hypoxic cell radiosensitizers.

## Key facts

- **NIH application ID:** 3179785
- **Project number:** 5R01CA040172-03
- **Recipient organization:** DUKE UNIVERSITY
- **SAM.gov UEI:** TP7EK8DZV6N5
- **Principal Investigator:** Randy L Jirtle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $117,224
- **Award type:** 5
- **Project period:** 1985-07-01 → 1988-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179785

## Citation

> US National Institutes of Health, RePORTER application 3179785, RADIOBIOLOGY OF RAT AND HUMAN HEPATOCYTES (5R01CA040172-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179785. Licensed CC0.

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