MECHANISMS OF CHEMICAL LYMPHOMAGENESIS

  • Lenz, Jack (PI)
  • Leinwand, Leslie (PI)
  • Lilly, Frank (PI)

Project: Research project

Project Details

Description

The goal of this research program is a comprehensive analysis of the
mechanisms whereby painting the skin of RF strain mice with the carcinogen,
3-methylcholanthrene (MCA), rapidly induces a near 100 percent incidence of
thymic lymphoma. Each project in the program will approach the problem
from a unique perspective, using different strategies and different
techniques ranging from studies in vivo through work with cultured lymphoma
cell lines to molecular studies by recombinant DNA techniques. Cells of
primary lymphomas and of lymphoma cell lines will be characterized
antigenically and virologically, and their capacity to elicit
transplantation immunity and specific cellular immune responses will be
determined. The nature of the nonmendelian, maternally transmitted factor
of RF mice which suppresses expression of endogenous murine leukemia virus
(MuLV) and spontaneous lymphoma will be studied. A recently identified
dominant gene which confers resistance to MCA induction of lymphoma--and
possibly to x-ray induction of lymphoma, as well--will be studied in order
to determine its map location and its mechanism of action. The role of
endogenous MuLV in MCA lymphomagenesis will be extensively explored. Cells
of RF lymphomas will be examined for new MuLV proviral information present
in their chromosomal DNA by comparison with DNA from embryo cells or from
normal lymphocytes, and any such new proviruses will be mapped within the
cellular genome. Recombinant DNA techniques will be used in the
characterization of cytoplasmic RNA transcripts containing viral
information will be made in an attempt to identify host genes (candidate
cellular oncogenes) and their products that are expressed as a result of
genomic rearrangements. A detailed examination of differences in overall
gene expression between normal and lymphoma cells will be made. The extent
to which findings in the system of MCA-induced RF lymphomas can be
generalized to other systems of lymphoma induction in this and other
strains of mice will be explored.
StatusFinished
Effective start/end date7/1/856/30/86

Funding

  • National Cancer Institute

ASJC

  • Applied Microbiology and Biotechnology
  • Genetics(clinical)
  • Genetics
  • Molecular Biology
  • Hematology
  • Cancer Research
  • History and Philosophy of Science
  • Toxicology
  • Immunology

Fingerprint Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.