Action site of the gene determining susceptibility to propylnitrosourea-induced thymic lymphomas in F344 rats.

To clarify whether the determining effect of the thymic lymphoma susceptible-1 (Tls-1) gene is on putative N-propyl-N-nitrosourea (PNU) target cells among T-lineage cells or on other host factors, we investigated the PNU-induced lymphomagenesis in transplantation chimeras between susceptible F344 and resistant LES strain rats. Administration of PNU to lethally irradiated (F344 x LES)F1 rats reconstituted with bone marrow cells from either F344 or LES parental rats invariably led to development of donor-origin thymic lymphomas. On the other hand, thymic lymphomas were induced in thymectomized F1 rats grafted with neonatal LES thymus, of which 4 out of 8 were of the donor origin. These observations indicate that the target cells of thymic lymphomagenesis of F344 and LES rats were equally susceptible to PNU provided they are in susceptible hosts and the LES thymus seems capable of supporting thymic lymphomagenesis, although this capability wanes with aging of the thymus. The effect of the Tls-1 gene, therefore, is neither on PNU susceptibility of the target cells nor on the capability of the thymus to support lymphomagenesis, but on other host factors either in or out of the thymus.