Existence of N-Nitroso-N-propylurea Target Cells in the Thymus of F344 Rats in Thymic Lymphomagenesis2

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Abstract
There are two hypotheses for location of first transformation of cells of T-cell lineage into preneoplastic cells from studies of leukemogenesis in mice; one is the bone marrow and another is the thymus. N-Nitroso-N-propylurea [(NPU) CAS: 816-57-9] induces high incidence of thymic lymphoma in F344 rats. In the present experiments, the location of NPU-target cells was examined in F344 rats. In the first experiment, bone marrow cells from NPU-treated male rats were inoculated into sublethally irradiated female rats. However, neither thymic nor other types of leukemias were induced in these rats. In the following experiment, thymectomized male rats received grafts sc with normal thymuses of age-matched female F344 rats. Continuous administration of NPU to the rats successfully induced 9 thymic lymphomas in the grafted thymuses. In 8 thymic lymphomas analyzed, 6 consisted of donor cells and the other 2 consisted of recipient cells. The present results from these 2 experiments strongly suggested that NPU-induced rat thymic lymphomas originate from intrathymic cells but not from bone marrow cells. In other words, target cells of leuke-mogenic activity of the chemical carcinogen NPU probably exist in the thymus of F344 rats.