# MURINE LYMPHOCYTE SCE MODEL FOR PREDICTING GENOTOXIC RIS

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 1987 · $105,113

## Abstract

Analysis of sister chromatid exchange (SCE) in peripheral blood lymphocytes
(PBLs) is commonly used as an indicator of genotoxic exposures of human
populations.  The primary goal of this proposal is to test the hypothesis:

The accumulation of unrepaired SCE-inducing lesions and their persistence
in PBLs, produced by repeated chemical exposure, are directly related to
the agent's tumorigenic activity.

Due to inherent limitations of human studies any association of acute or
persistently elevated SCEs in human PBL and genotoxic damage in critical
body tissues and/or carcinogenesis is, at best, inferred.  Therefore, as a
means of testing our hypothesis we describe a parellelogram approach which:

1. Compares murine and human PBL SCE responses to a known carcinogen,
L-phenylalanine mustard (L-PAM), and

2. Compares murine PBL SCE responses to responses in other critical tissues
following treatment of mice with chemicals of varying carcinogenic
activities.

For the first part of this study a very large L-PAM-treated patient SCE
data base is available from a local study.  This enables us to design
equivalent murine L-PAM treatment protocols in order to determine whether
the same general post-treatment trends in SCE responses are observed in
human and murine PBLs.

In the second part of the study, L-PAM and, if time permits, other
alkylating agents will be administered to mice using the established lung
adenoma assay protocol.  SCEs will be evaluated in PBLs, spleen, lymph
node, and thymus lymphocytes at various time intervals (24 hrs - 15 wks)
after the last treatment.  The following questions will be addressed:

Successful evaluation of the proposed animal model will provide the basis
for future studies.  For example, a chemical which produces ambiguous SCE
results in humans can be more completely evaluated at high and low doses in
the animal model in order to determine human genotoxic risk.  In addition,
new chemicals can be evaluated in the animal model in order to predict
genotoxic risk prior to wide spread human exposure.

## Key facts

- **NIH application ID:** 3178320
- **Project number:** 5R01CA039401-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **SAM.gov UEI:** MKAGLD59JRL1
- **Principal Investigator:** MARY K CONNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $105,113
- **Award type:** 5
- **Project period:** 1985-09-01 → 1989-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178320

## Citation

> US National Institutes of Health, RePORTER application 3178320, MURINE LYMPHOCYTE SCE MODEL FOR PREDICTING GENOTOXIC RIS (5R01CA039401-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178320. Licensed CC0.

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