title: 7,12-DMBA-induced rat leukemia: a review with insights into future research.
abstract: 7,12-Dimethylbenz[a]anthracene (DMBA) elicits leukemia in Long-Evans rats (LE). This leukemia is mostly erythroblastic and 30% of leukemias have total and partial trisomy of #2 chromosome and the rest have diploid karyotype. The common duplication site is in 2q26-q34 and N-ras gene is located in 2q34. 7,8,12-Trimethylbenz[a]anthracene (TMBA) also induces similar leukemias. These leukemias reveal a highly specific mutation of N-ras gene as in human leukemias. N-ras mutation is induced 48h after DMBA treatment. Wild type N-ras allele is frequently lost in diploid leukemias but not in trisomy type. Therefore, a gene dosage problem related to the mutant N-ras gene is involved in development of leukemia. Some secondary genetic rearrangements involving abl and H-ras are also observed in cultured leukemia cells. DMBA-induced chromosome aberrations as well as leukemia are enhanced by erythropoietin and blocked by Sudan III given prior to DMBA treatment. This leukemia will provide an important tool for chemical carcinogenesis and leukemia studies.
authors.affiliation: Shiga Medical Center Research Institute, Moriyama, Shiga, Japan. sugiyama@shigamed.jp
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Osaka
authors.forename: Kenichi
authors.initials: K
authors.lastname: Koami
authors.forename: Sakan
authors.initials: S
authors.lastname: Maeda
authors.forename: Norifumi
authors.initials: N
authors.lastname: Ueda
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D004195:Disease Models, Animal; D007938:Leukemia / Q000139:chemically induced* / Q000209:etiology / Q000235:genetics; D051381:Rats; D012106:Research / Q000639:trends; D018631:ras Proteins / Q000235:genetics
chemical_list: D015127:9,10-Dimethyl-1,2-benzanthracene; D018631:ras Proteins