CHEMICALLY INDUCED LYMPHOMAS: EXPRESSION OF LYMPHOCYTE DIFFERENTIATION ANTIGENS AND ENDOGENOUS RETROVIRUS GENES

Abstract

Inbred mice of the RF strain display a low incidence of spontaneous lymphoma that rarely occurs before one year of age, but are extremely susceptible to lymphomagenesis by chemical carcinogens. Percutaneous treatment with 3-methylcholanthrene (MCA) results in nearly a 100% incidence of thymic lymphomas by six to eight months of age. Although some RF mice express infectious ecotropic virus late in life, neither xenotropic nor MCF viruses have been isolated and there is no direct relationship between infectious virus expression and chemical lymphomagenesis in RF mice. Oncogenic MCF viruses are believed to result from recombination between endogenous ecotropic and xenotropic-related sequences and appear to represent a proximal cause in murine tumorigenesis, although infectious virus expression does not appear necessary for maintenance of the tumor state.;Studies were undertaken to examine the nature of MCA-induced lymphomas at the cellular level and to ascertain if expression of endogenous virus-related genes plays a role in the etiology of such tumors. Cells from primary lymphomas and tumors in culture, as well as normal thymocytes, were studied for surface expression of lymphocyte differentiation antigens by direct or indirect immunofluorescence in conjunction with fluorescence-activated cell sorter (FACS) analysis. Cells from these populations were also analyzed for expression of endogenous viral genes by infectious assays, electron microscopy, FACS analysis and metabolic labeling.;The results indicate that MCA-induced tumor cells develop in lymphocytes of the T-cell lineage and express Lyt-1, Lyt-2, H-2D, H-2K and Oa-1. Phenotypically, tumor cells resemble a small subpopulation of cortisone resistant medullary thymocytes and a subset of T-cells that function in feedback suppression. The relative uniformity of the tumor cell phenotype suggests that a unique target cell for chemical lymphomagenesis may exist.;Thymocytes from normal RF mice display an age-associated increase in surface expression of MuLV gag and env antigens and synthesize an unusual envelope protein of 50 kilodaltons. The expression of MCF/xenotropic-related envelope proteins on normal thymocytes and on tumor cells in the absence of infectious virus production raises the possibility that MCF/xeno-related sequences paly a role in MCA lymphomagenesis in RF mice.