Thymic Lymphomas Induced by N‐Propyl‐N‐Nitrosourea (PNU) in the BUF/Mna Rat, an Inbred Strain with a High Incidence of Spontaneous Thymoma

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Abstract
N-Propyl-N-nitrosourea (PNU) is known to be a strong leukemogen, inducing myelogenous leukemia or thymic lymphoma in some strains of rat. The thymic lymphomagenic effect of PNU has been demonstrated in F344 rats. On the other hand, the BUF/Mna rat has been established as an inbred strain that develops spontaneous thymomas after one year of age. In the present experiment, PNU was continuously administered in drinking water to male and female BUF/Mna rats starting at 5 weeks of age. Thymic lymphomas were induced in all PNU-treated rats with an average latent period as short as 14 experimental weeks. These results show the high susceptibility of BUF/Mna rat to the lymphomagenic activity of PNU. The BUF/Mna rat is an ideal strain for studies on epithelial cell-lymphocyte interaction, not only in the development of thymic lymphomas but also in that of spontaneous thymoma. Karyotypes of twelve primary thymic lymphomas induced by PNU were analyzed for chromosomal abnormalities. Chromosomal abnormalities were often found in chromosomes 11 and 2. In some types of abnormality, dup (11q) and del(2q) were most frequently observed. In addition, trisomy of chromosome 7, on which the c-myc gene is mapped, was observed in five lymphomas, and monosomy of chromosomes 20 and X in six and five cases, respectively, though these changes were generally observed in a minor cell population in each case.