Role of the thymus in propylnitrosourea-induced thymic lymphomagenesis in F344 rats

Abstract

The role of the thymus in propylnitrosourea (PNU)-induced thymic lymphomagenesis was studied in F344 rats with genetically determined high susceptibility. The thymus was absolutely required for thymic lymphomagenesis, since thymectomy prior to or after PNU treatment abolished lymphomagenesis, whereas grafting of a normal neonatal thymus before PNU treatment restored it. Exposure to PNU for 42 days resulted in the appearance of potentially lymphomatous cells first in the thymus, and overt T-lymphomas subsequently appeared. Such cells seemed to be thymus-dependent, since intrathymic transfer of the thymus cells from 42-day PNU-treated rats induced T-lymphomas much more efficiently than intravenous transfer. Further, grafting of the thymus from 42-day PNU-treated rats into thymectomized rats resulted in T-lymphomas of donor origin without additional PNU treatment. Cells from the spleen or bone marrow from the same donors did not give rise to T-lymphomas irrespective of the route of cell transfer and sublethal irradiation of the recipients. Morphologically atypical cell foci were detected first on the 28th day in the thymus and were most pronounced during the 35th-42nd days. Therefore, the thymus is the essential organ in which the early events of PNU-induced rat T-lymphomagenesis take place.