Relation between development of leukemia and duration of N-nitroso-N-ethylurea treatment in DONRYU rats

N-Nitroso-N-ethylurea (NEU; CAS: 759-73-9) is a strong leukemogen that induces erythroblastic leukemia in inbred DONRYU rats. In the present experiments, relationships between development of leukemia, duration of NEU treatment, and sequential changes in the hematopoietic organs during carcinogen administration were examined. In experiment 1, groups of rats were given a 400-ppm NEU solution for 0, 2, 4, 6, 8, or 10 weeks, and the resultant incidence of leukemias was 0, 26, 40, 75, 95, and 100%, respectively. Of the various types of leukemia, the erythroblastic type was observed in 0, 0, 20, 40, 95, and 90% of rats, respectively. The average latent period showed an inverse correlation with the duration of NEU treatment. In experiment 2 the animals were divided into carcinogen-treated and control groups, and rats were sacrificed periodically for histopathologic examination. In the experimental group, the bone marrow became hypoplastic soon after commencement of NEU treatment and at the 6th week became severely aplastic, thereafter recovering slightly. At the 10th week, 2 rats out of 5 examined were leukemic. Relationships between incidence of leukemia, duration of NEU treatment, and sequential changes of the bone marrow during carcinogen administration are discussed.