# MECHANISMS OF MNU INDUCED LYMPHOMA IN AKR MICE

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 1992 · $136,506

## Abstract

The carcinogen N-methyl-N-nitrosourea (MNU) induces thymic lymphoma
development in various inbred mouse strains.  The AKR strain is
particularly susceptible, experiencing a higher incidence and shorter
latency (2-3 months) for MNU-induced lymphoma development than other
inbred mouse strains.  The molecular basis for the enhanced
susceptibility of the AKR strain is not clear.  However, in contrast to
most inbred strains, untreated AKR mice develop spontaneous thymic
lymphoma after 8 months of age due to the generation of recombinant
oncogenic murine leukemia viruses (MuLV).  Several reports implicate
endogenous MuLV as co-factors in chemical carcinogenesis.  Therefore, I
have proposed that the enhanced susceptibility of AKR mice to MNU-induced
lymphomagenesis involves participation of endogenous MuLV in the
multistage pathway resulting in neoplastic transformation.  Recently, we
found aberrant expression of functional interleukin-2 receptors (IL-2Rs)
on MNU-induced lymphomas.  This is interesting since these tumors
correspond to immature T-cells that normally down-regulate IL-2R
expression.  Furthermore, preliminary data suggest that IL-2Rs on
MNU-induced lymphomas are associated with the MuLV envelop glycoprotein,
gp70.  Similar observations have been made in Friend MuLV induced
erythroleukemia in which binding of a defective MuLV envelop protein gp55
to erythropoietin receptors in immature erythroblasts induces prolonged
proliferation of the preneoplastic target population.  In view of this
precedent and preliminary data from our lab, I am proposing that NM
activates expression of endogenous MuLV gp70 which can bind to and
stimulate lL-2Rs on initiated thymocytes.  This event is likely to
trigger accelerated expansion and progression of the target population
explaining, in part, the predisposition of the AKR strain to develop a
high incidence of early appearing MNU-induced lymphomas.  The specific
aims for this proposal are: (1).  To characterize the IL-2Rs expressed on
MNU-induced lymphomas with respect to number, affinity, polypeptide chain
structure and functional activity. (2.) To assess IL-2R protein and mRNA
expression in specific thymocyte subsets at various intervals after MNU
treatment and isolate IL-2R bearing cells for analysis of clonality and
oncogene activation. (3.) To determine if there is a specific cell
surface and/or intracellular association between IL-2Rs and MuLV gp70
molecules in MNU-induced lymphomas as well as in thymocyte subsets
obtained at intervals after MNU treatment. (4.) To identify, using a
panel of monoclonal antibodies, the class(es) of endogenous MuLV gp70
molecules expressed on lymphomas and preneoplastic thymocytes as a
consequence of MNU activation and to isolate relevant gp70 molecules for
analysis of IL-2R binding and stimulation. (5.) To molecularly clone
endogenous MuLV sequences that encode the gp70 subclass defined by
specific aim #4 and develop constructs for future retroviral mediated
gene transfer.

## Key facts

- **NIH application ID:** 3175859
- **Project number:** 2R01CA037912-07
- **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:** 1992
- **Award amount:** $136,506
- **Award type:** 2
- **Project period:** 1984-08-01 → 1997-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175859

## Citation

> US National Institutes of Health, RePORTER application 3175859, MECHANISMS OF MNU INDUCED LYMPHOMA IN AKR MICE (2R01CA037912-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175859. Licensed CC0.

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