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Detection of activated proto-oncogenes in N-nitrosodiethylamine-induced liver tumors: a comparison between B6C3F1 mice and Fischer 344 rats |
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| Authors: | Stowers, S.Jill Wiseman, Roger W. Ward, Jerrold M. Miller, Elizabeth C. Miller, James A. Anderson, Marshall W. Eva, Alessandra |
| Affiliation: | National Institute of Environmental Health Sciences PO Box 12233, Research Triangle Park, NC 27709, USA 1Laboratory of Biochemical Risk Analysis PO Box 12233, Research Triangle Park, NC 27709, USA 2Laboratory of Molecular Carcinogenesis PO Box 12233, Research Triangle Park, NC 27709, USA 3Laboratory of Comparative Carcinogenesis, Division of Cancer Etiology, National Cancer Institute Frederick, MD 21701, USA 4McArdle Laboratory for Cancer Research, University of Wisconsin Madison, WI 53706, USA 5Laboratory of Cellular and Molecular Biology, National Institutes of Health Bethesda, MD 20205, USA |
| Abstract: | DNA from B6C3F1 mouse and Fischer 344 rat liver tumors inducedby N-nitrosodiethylamine (DEN) were examined for the abilityto induce morphological transformation of NIH3T3 cells. DNAsfrom 14 of 33 of the mouse liver tumors induced by a singleinjection of DEN at 12 or 15 days of age were positive in thisassay while DNA from only one of 28 DEN-induced rat liver tumorswas active. Southern blot analysis of the NIH3T3 transformantsderived from the mouse liver tumors revealed amplified and/orrearranged restriction fragments homologous to the H-ras proto-oncogene.DNA from two independent foci induced by the rat tumor DNA didnot hybridize to probes for members of the ras gene family orc-raf. Activating mutations in the H-ras genes from the DEN-inducedmouse liver tumors were characterized by selective oligonucleotidehybridization and the detection of a new XbaI restriction siteby Southern blot analysis. In activated H-ras genes from theDEN-induced mouse liver tumor DNA, seven of 14 had a CG AT transversionat the first base of the 61st codon, three of 14 had an ATGCtransition and four of 14 had the ATTA transversion at the secondbase of codon 61. This spectrum of mutations is very similarto that recently observed in activated H-ras genes found inspontaneously occurring B6C3F1 mouse liver tumors. Taken together,the data suggest that the DEN-induced rat and mouse liver carcinogenesismay involve genetic targets other than or in addition to theH-ras gene. |
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