Direct mutagenesis of Ha-ras-1 oncogenes by N-nitroso-N-methylurea during initiation of mammary carcinogenesis in rats

Nature. 1985 May 30-Jun 5;315(6018):382-5. doi: 10.1038/315382a0.


Induction of mammary carcinomas in rats by a single exposure to a carcinogen during sexual development often involves malignant activation of the Ha-ras-1 locus. Each of the Ha-ras-1 oncogenes present in tumours induced by N-nitroso-N-methylurea, but not in those induced by 7,12-dimethylbenz(a)anthracene, became activated by the same G----A transition, the type of mutation induced by N-nitroso-N-methylurea. These results are consistent with the notion that Ha-ras-1 oncogenes are directly activated by the carcinogen during initiation of neoplasia.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / toxicity
  • Animals
  • Base Sequence
  • Female
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / genetics*
  • Methylnitrosourea / toxicity*
  • Mutation / drug effects*
  • Nitrosourea Compounds / toxicity*
  • Oncogenes*
  • Rats


  • Nitrosourea Compounds
  • 9,10-Dimethyl-1,2-benzanthracene
  • Methylnitrosourea