# EXPERIMENTAL RADIOTHERAPY, CARCINOGENESIS, AND PROTECTOR

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 1988 · $226,403

## Abstract

The objectives of this investigation are (1) to characterize the response
of cells from normal and tumor tissue to ionizing radiation and/or selected
chemotherapeutic agents as a function of therapeutic protocol and (2) to
use chemical modifiers such as radioprotectors to elucidate the underlying
mechanisms of action leading to the observed effects.  This study will
focus on maximizing therapeutic gain while minimizing the inductive effects
of radiation on the processes of mutagenesis and carcinogenesis in normal
tissues exposed during treatment.  Both in vitro and in vivo cell systems
will be used to assess the effectiveness of selected radioprotectors, which
include 2-[(aminopropyl)amino] ethanethiol (WR1065) and
[S-2-(3-aminopropylamino) ethyl phosphorothioic acid] (WR2721).
Mutagenesis studies will be performed with V79 Chinese hamster cells by
assaying for radiation and/or drug-induced mutations at the
hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus as a function
of radioprotector concentration and timing of administration.  In vivo
systems will include a neonatal Sprague Dawley rat system used to assess,
in relatively short periods of time, the induction of preneoplastic lesions
(altered hepatocyte foci) as a function of exposure to radiation,
chemotherapy agents, and/or radioprotectors.  Tumor systms to be used to
assess therapeutic gain include a methylcholanthrene-induced fibrosarcoma
(FSa), a spontaneously arisen fibrosarcoma (NFSA), and a spontaneously
arisen mammary carcinoma (MCa-K).  These tumors will be grown in both
defined flora and conventionally maintained C3Hf/Sed mice.  Time dose
studies will be performed to assess therapeutic effectiveness with respect
to both tumor control and induction of mutagenic and carcinogenic processes
in non-neoplastic cell systems.  DNA damage and repair will be measured
through the techniques of alkaline and neutral elution.  Where required,
biophysical techniques such as centrifugal elutriation will be used to
isolate unique cell populations for study.  Through the integration of
these systems it will be possible to evaluate the usefulness of chemical
modifiers such as radioprotectors to not only improve therapeutic gain but
also significantly reduce the associated risk of therapy-induced
mutagenesis and carcinogenesis in exposed normal tissues.

## Key facts

- **NIH application ID:** 3175284
- **Project number:** 5R01CA037435-06
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **SAM.gov UEI:** ZUE9HKT2CLC9
- **Principal Investigator:** DAVID J. GRDINA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $226,403
- **Award type:** 5
- **Project period:** 1983-09-30 → 1989-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175284

## Citation

> US National Institutes of Health, RePORTER application 3175284, EXPERIMENTAL RADIOTHERAPY, CARCINOGENESIS, AND PROTECTOR (5R01CA037435-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175284. Licensed CC0.

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