# MECHANISMS OF MNU INDUCED LYMPHOMA IN AKR MICE

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 1989 · $103,157

## Abstract

Oncogenesis is a multistep process during which sequential damage to
critical cellular genes (proto-oncogenes) eventually generates a
malignant clone with unrestrained growth and metastatic properties.  Each
genetic alteration is thought to represent a single step in the process
of tumor development since activation of more than one oncogene is
generally required to achieve malignant transformation.  The hypothesis
that different activated oncogenes synergize in tumor initiation and/or
promotion has received substantial experimental support.  This concept
supports the notion that different etiologic agents such as viruses and
chemicals induce genetic damage in distinct, yet functionally cooperative
genetic loci.  Although it seems reasonable to propose that proviral
insertion and carcinogen mediated point mutation could activate
complimentary oncogenes, the potential role of endogenous retroviruses in
chemical carcinogenesis is not clear.  An excellent model to address this
issue is the AKR mouse strain in which endogenous murine leukemia viruses
(MuLV) induce "spontaneous" thymic lymphomas.  Injection of young mice
with N-methyl-N-nitrosourea (MNU) accelerates lymphomagenesis.  The AKR
strain develops MNU induced lymphomas with higher incidence and shorter
latent period than low lymphoma incidence strains, suggesting a
cooperative interaction between MNU and endogenous MuLVs.  Since we find
that MNU induced AKR lymphomas contain newly acquired proviruses that
confer a selective growth advantage, we propose that endogenous MuLVs
synergize with MNU by promoting a more malignant phenotype perhaps
through specific oncogene activation.  The aims of this project are: 1.
to determine whether somatically acquired proviruses confer enhanced
growth and/or metastatic properties on MNU induced lymphomas.  2. to
define the molecular structure of somatically acquired proviruses.  3. to
identify new oncogenes activated via proviral insertion.  4. using a
novel approach involving multiparameter flow cytometry and cell sorting
early neoplastic cells will be isolated at intervals from thymi of MNU
treated mice for analysis of: clonality; growth potential in vivo and in
vitro; proviral integrations; and molecular alterations in oncogene
structure or expression.  Long term goals are also described to indicate
the future direction of this project.

## Key facts

- **NIH application ID:** 3175858
- **Project number:** 2R01CA037912-04A2
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **SAM.gov UEI:** S3GMKS8ELA16
- **Principal Investigator:** Ellen R Richie
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $103,157
- **Award type:** 2
- **Project period:** 1984-08-01 → 1992-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175858

## Citation

> US National Institutes of Health, RePORTER application 3175858, MECHANISMS OF MNU INDUCED LYMPHOMA IN AKR MICE (2R01CA037912-04A2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175858. Licensed CC0.

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