title: ras and p53 genes are infrequently involved in N-nitroso-N-butylurea (NBU)-induced rat leukemia.
abstract: 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.
authors.affiliation: Department of Pathology, Faculty of Medicine, Kyoto University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Osaka
authors.forename: T
authors.initials: T
authors.lastname: Tsuruyama
authors.forename: K
authors.initials: K
authors.lastname: Koami
authors.forename: S
authors.initials: S
authors.lastname: Matsuo
authors.forename: T
authors.initials: T
authors.lastname: Sugiyama
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D005091:Exons; D016158:Genes, p53 / Q000187:drug effects*; D011905:Genes, ras / Q000187:drug effects*; D004915:Leukemia, Erythroblastic, Acute / Q000139:chemically induced / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000139:chemically induced / Q000235:genetics*; D009607:Nitrosourea Compounds / Q000633:toxicity*; D017354:Point Mutation; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D002273:Carcinogens; D009607:Nitrosourea Compounds; D015127:9,10-Dimethyl-1,2-benzanthracene; C002738:N-nitrosobutylurea