Detection of activated proto-oncogenes in N-nitrosodiethylamine-induced liver tumors: A comparison between B6C3F1 mice and Fischer 344 rats

S. J. Stowers, R. W. Wiseman, J. M. Ward, E. C. Miller, J. A. Miller, M. W. Anderson, A. Eva

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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 restriciton 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.

Original languageEnglish
Pages (from-to)271-276
Number of pages6
JournalCarcinogenesis
Volume9
Issue number2
Publication statusPublished - 1988

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ASJC Scopus subject areas

  • Cancer Research
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Physiology
  • Behavioral Neuroscience

Cite this

Stowers, S. J., Wiseman, R. W., Ward, J. M., Miller, E. C., Miller, J. A., Anderson, M. W., & Eva, A. (1988). Detection of activated proto-oncogenes in N-nitrosodiethylamine-induced liver tumors: A comparison between B6C3F1 mice and Fischer 344 rats. Carcinogenesis, 9(2), 271-276.