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)-in duced erythroblastic leukemias which consistently have an A to T trans version at the second base of codon 61 in N-ras. By continuous NBU tre atment for 120-150 days, 14 primary leukemias were induced in Long-Eva ns rats. Myeloblastic leukemia cells predominantly increased in all ra ts except in one case which predominantly had erythroblastic leukemia cells. Point mutations of Ha-, Ki-, N-ras and p53 were determined afte r 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 infrequentl y involved in NBU-induced leukemias. The genetic target of NBU during leukemogenesis seemed to be different from that of DMBA. (C) 1998 Else vier Science Ireland Ltd.