# EXPERIMENTAL RADIOTHERAPY, CARCINOGENESIS, AND PROTECTOR

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 1990 · $242,883

## 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 process of
mutagenesis 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 both repair-
proficient (K1, AA8) and repair-deficient (xrs-5, EM9) CHO cell lines,
as well as with a human lymphoblastoid cell line designated L33, by
assaying for radiation and/or drug-induced mutations at the
hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus as a
function of radioprotector chemicals on these processes will also be
determined.  Tumor systems 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.  DNA damage and repair will be measured
through the 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:** 3175285
- **Project number:** 5R01CA037435-08
- **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:** 1990
- **Award amount:** $242,883
- **Award type:** 5
- **Project period:** 1983-09-30 → 1994-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175285

## Citation

> US National Institutes of Health, RePORTER application 3175285, EXPERIMENTAL RADIOTHERAPY, CARCINOGENESIS, AND PROTECTOR (5R01CA037435-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175285. Licensed CC0.

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