title: Detection of activated proto-oncogenes in N-nitrosodiethylamine-induced liver tumors: a comparison between B6C3F1 mice and Fischer 344 rats.
abstract: DNA from B6C3F1 mouse and Fischer 344 rat liver tumors induced by N-nitrosodiethylamine (DEN) were examined for the ability to induce morphological transformation of NIH3T3 cells. DNAs from 14 of 33 of the mouse liver tumors induced by a single injection of DEN at 12 or 15 days of age were positive in this assay while DNA from only one of 28 DEN-induced rat liver tumors was active. Southern blot analysis of the NIH3T3 transformants derived from the mouse liver tumors revealed amplified and/or rearranged restriction fragments homologous to the H-ras proto-oncogene. DNA from two independent foci induced by the rat tumor DNA did not hybridize to probes for members of the ras gene family or c-raf. Activating mutations in the H-ras genes from the DEN-induced mouse liver tumors were characterized by selective oligonucleotide hybridization and the detection of a new XbaI restriction site by Southern blot analysis. In activated H-ras genes from the DEN-induced mouse liver tumor DNA, seven of 14 had a CG----AT transversion at the first base of the 61st codon, three of 14 had an AT----GC transition and four of 14 had the AT----TA transversion at the second base of codon 61. This spectrum of mutations is very similar to that recently observed in activated H-ras genes found in spontaneously occurring B6C3F1 mouse liver tumors. Taken together, the data suggest that the DEN-induced rat and mouse liver carcinogenesis may involve genetic targets other than or in addition to the H-ras gene.
authors.affiliation: National Institute of Environmental Health Sciences, Laboratory of Biochemical Risk Analysis, Research Triangle Park, NC 27709.
authors.forename: S J
authors.initials: SJ
authors.lastname: Stowers
authors.forename: R W
authors.initials: RW
authors.lastname: Wiseman
authors.forename: J M
authors.initials: JM
authors.lastname: Ward
authors.forename: E C
authors.initials: EC
authors.lastname: Miller
authors.forename: J A
authors.initials: JA
authors.lastname: Miller
authors.forename: M W
authors.initials: MW
authors.lastname: Anderson
authors.forename: A
authors.initials: A
authors.lastname: Eva
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D003062:Codon; D004262:DNA Restriction Enzymes; D004273:DNA, Neoplasm / Q000235:genetics*; D004052:Diethylnitrosamine; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D009693:Nucleic Acid Hybridization; D011519:Proto-Oncogenes; D051381:Rats; D011916:Rats, Inbred F344; D014162:Transfection
chemical_list: D003062:Codon; D004273:DNA, Neoplasm; D004052:Diethylnitrosamine; D004262:DNA Restriction Enzymes