Age-dependent induction of thymic lymphomas by N-propyl-N-nitrosourea in the F344/DuCrj rat

N-Propyl-N-nitrosourea (PNU) is one of the most potent thymic-lymphomagenic agents in rats. Our previous experiments strongly suggested that leukemogenic viruses were not the cause of thymic lymphomas in rats and that target cells of PNU exist in the thymus but not in the bone marrow. On the other hand, the role of retrovirus in lymphomagenesis is undeniable in mice. Therefore, chemically induced rat thymic lymphoma provides a good model to analyse lymphomagenesis without viral implications. In the present experiment 1, we investigated the relationship between the age of animal at commencement of PNU treatment and the incidence of thymic lymphomas. Incidences of thymic lymphomas were 100, 100, 80 and 18, and average latent periods were 15.1, 18.7, 25.4 and 27.3 weeks after the start of PNU-treatment, in 5-, 10-, 20- and 40-week-old groups, respectively. In experiment 2, rats were sacrificed postnatally at 5, 10, 20, 30 and 40 weeks each, and thymus weight, number of thymocytes in the thymus, frequency of mitosis, and percentage of OX-7 (Thy 1.1), OX-8 (CD8), or W3/25 (CD4) positive cells, were examined cytologically. Thymus weight, number of cells in the thymus and mitotic index were maximum at 10 weeks old, and thereafter decreased gradually. No marked changes were observed in the ratio of each cell-surface marker positive cell. These results indicate that induction of thymic lymphomas by PNU is very closely related with the total number of mitotic cells in the thymus. Thus, chemical induction of rat thymic lymphoma reflects an age-dependent function of the thymus.