N-RAS MUTATION IN 7,12-DIMETHYLBENZ[A]ANTHRACENE (DMBA)-INDUCED ERYTHROLEUKEMIA IN LONG-EVANS RATS

Intravenous injections of 7,12-dimethylbenz[a]anthracene (DMBA) induce erythroblastic leukemia (erythroleukemia) with No.2 trisomy in Long-E vans rats. Activation of some oncogenes such as abl and Ha-ras has bee n reported to occur in relation to the secondary chromosomal transloca tions, In the present studies, a consistent type of mutation, A to T t ransversion in codon 61 of N-ras gene, was found in all of 6 cultured leukemia cell lines and 5 primary leukemias induced by DMBA. The N-ras mutation was also found in bone marrow cells of 2 out of 8 preleukemi as. On the contrary, no mutation was observed in Ha- and Ki-ras genes in all leukemias and preleukemias. The consistent occurrence of above N-ras mutation in leukemias indicates that it plays an important role in DMBA-leukemogenesis.