ras and p53 genes are infrequently involved in N-nitroso-N-butylurea (NBU)-induced rat leukemia

Chemically-induced rodent tumor models help us to understand a series of genetic changes during carcinogenesis. In this study, we present N-nitroso-N-butylurea (NBU)-induced rat leukemia and compare it with the genetic alterations found in 7,12-dimethylbenz[a]anthracene (DMBA)-induced erythroblastic leukemias which consistently have an A to T transversion at the second base of codon 61 in N-ras. By continuous NBU treatment for 120–150 days, 14 primary leukemias were induced in Long–Evans rats. Myeloblastic leukemia cells predominantly increased in all rats except in one case which predominantly had erythroblastic leukemia cells. Point mutations of Ha-, Ki-, N-ras and p53 were determined after RNA was transcribed into cDNA and this cDNA was used as a substrate for polymerase chain reaction (PCR) which was eventually sequenced. No abnormalities in exons 1 and 2 of Ha-, Ki- and N-ras were detected in all leukemias. In the p53 gene, an A to C transition was found at the second base of codon 198 (Asn-Thr) in one leukemia, but others had no mutation. These results suggest that ras and p53 genes are infrequently involved in NBU-induced leukemias. The genetic target of NBU during leukemogenesis seemed to be different from that of DMBA.