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Induction of multiple independent T-cell lymphomas in rats inoculated with MOloney murine leukemia virus
A Bellacosa1, P A Lazo, S E Bear
1Department of Medicine, Fox Chase Cancer Center, Philadelphia, PA 19111.
Abstract:
Tumor cell DNA derived from different lymphoid organs of 30 rats serially inoculated at birth with Moloney murine leukemia virus (MoMuLV) was examined by Southern blot analysis and hybridization to the following DNA probes: MoMuLV long terminal repeat (LTR), Moloney leukemia virus integration regions 1, 2, 3, and 4 (Mlvi-1, Mlvi-2, Mlvi-3, and Mlvi-4), T-cell receptor beta locus, and immunoglobulin heavy chain locus. This analysis revealed that the tumors segregating in different lymphoid organs in 10% of the animals were clonally unrelated. These findings are consistent with the hypothesis that the MoMuLV-induced rat thymic lymphomas are polyclonal in origin. At least two factors may be responsible for this phenomenon: (i) increase in the number of the available target cells in virus-infected animals, and (ii) genetic instability associated with provirus integration in the developing premalignant clones.
Insights
Moloney murine leukemia virus (MoMuLV) can cause rat thymic lymphomas. Studies suggest these MoMuLV-induced lymphomas originate from multiple cell types, indicating a polyclonal origin.
Area of Science:
- Virology
- Oncology
- Molecular Biology
Background:
- Moloney murine leukemia virus (MoMuLV) is known to induce thymic lymphomas in rats.
- Understanding the cellular origin of these tumors is crucial for comprehending viral oncogenesis.
Purpose of the Study:
- To investigate the clonal origin of Moloney murine leukemia virus (MoMuLV)-induced rat thymic lymphomas.
- To determine if these lymphomas arise from a single cell (monoclonal) or multiple cells (polyclonal).
Main Methods:
- Southern blot analysis and DNA hybridization were used to examine tumor cell DNA from rats inoculated at birth with MoMuLV.
- Probes included MoMuLV long terminal repeat (LTR), Moloney leukemia virus integration regions (Mlvi-1 to Mlvi-4), T-cell receptor beta locus, and immunoglobulin heavy chain locus.
Main Results:
- Analysis revealed that in 10% of the animals, tumors from different lymphoid organs were clonally unrelated.
- This indicates that multiple distinct cell populations can give rise to lymphomas within the same animal.
Conclusions:
- The findings support the hypothesis that MoMuLV-induced rat thymic lymphomas are polyclonal in origin.
- Potential contributing factors include an increased number of target cells and genetic instability from provirus integration.
