Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA031855-07
Application #
3093437
Study Section
Cancer Special Program Advisory Committee (CAK)
Project Start
1982-07-01
Project End
1990-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461

  Publications

Borriello, F; Krauter, K S (1990) Reactive site polymorphism in the murine protease inhibitor gene family is delineated using a modification of the PCR reaction (PCR + 1). Nucleic Acids Res 18:5481-7
Montgomery, K T; Tardiff, J; Reid, L M et al. (1990) Negative and positive cis-acting elements control the expression of murine alpha 1-protease inhibitor genes. Mol Cell Biol 10:2625-37
Lenz, J; Okenquist, S A; LoSardo, J E et al. (1990) Identification of a mammalian nuclear factor and human cDNA-encoded proteins that recognize DNA containing apurinic sites. Proc Natl Acad Sci U S A 87:3396-400
Silver, G; Reid, L M; Krauter, K S (1990) Dexamethasone-mediated regulation of 3-methylcholanthrene-induced cytochrome P-450d mRNA accumulation in primary rat hepatocyte cultures. J Biol Chem 265:3134-8
Kraft, R; Ishizaka, S T; Okenquist, S A et al. (1989) Absence of mouse mammary tumor virus proviral amplification in chemically induced lymphomas of RF/J mice. J Virol 63:3200-4
Silver, G; Krauter, K S (1988) The Ah domain of the mouse. Induction of proteins by the carcinogen 3-methylcholanthrene. Biochem J 252:159-65
Silver, G; Krauter, K S (1988) Expression of cytochromes P-450c and P-450d mRNAs in cultured rat hepatocytes. 3-Methylcholanthrene induction is regulated primarily at the post-transcriptional level. J Biol Chem 263:11802-7
Dasgupta, U B; Lilly, F (1988) Chemically induced murine T lymphomas: continued rearrangement within the T-cell receptor beta-chain gene during serial passage. Proc Natl Acad Sci U S A 85:3193-7
Iqbal, M A; Chinsky, J; Didamo, V et al. (1987) Replication of proto-oncogenes early during the S phase in mammalian cell lines. Nucleic Acids Res 15:87-103
Ishizaka, S T; Lilly, F (1987) Genetically determined resistance to 3-methylcholanthrene-induced lymphoma is expressed at the level of bone marrow-derived cells. J Exp Med 166:565-70

Showing the most recent 10 out of 13 publications