These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Mutagenesis of the K-ras protooncogene in mouse lung tumors induced by N-ethyl-N-nitrosourea or N-nitrosodiethylamine.
    Author: You M, Wang Y, Lineen AM, Gunning WT, Stoner GD, Anderson MW.
    Journal: Carcinogenesis; 1992 Sep; 13(9):1583-6. PubMed ID: 1394843.
    Abstract:
    The role of ras gene activation in the development of lung tumors induced by N-ethyl-N-nitrosourea (ENU) and N-nitrosodiethylamine (DEN) was evaluated in the A/J mouse, a strain susceptible to chemically induced lung tumors. DNAs isolated from both ENU- and DEN-induced lung tumors were screened for activating mutations in the K-ras gene by utilizing the polymerase chain reaction (PCR) and direct sequence analysis. Mutations in the K-ras gene were detected in 11 of 11 ENU-induced tumors and 23 of 28 DEN-induced tumors. In ENU-induced tumors, there were three GC----AT transitions in the second base of codon 12, and seven AT----GC transitions and one AT----TA transversion in the second base of codon 61. A similar spectrum of K-ras mutations was observed in DEN-induced lung tumors: five GC----AT transitions and two GC----TA transversions in the second base of codon 12, and sixteen AT----GC transitions at the second base of codon 61. Ninety-one percent (31/34) of the observed mutations are consistent with the formation of the promutagenic O4-ethylthymine and O6-ethylguanine adducts in DNA. Therefore, lung tumors from the A/J mouse induced by DEN and ENU could be initiated by the interaction of reactive metabolites with specific sites in the K-ras gene. This is the first clear example of activation of the K-ras gene by ethylating agents in a rodent lung tumor system.
    [Abstract] [Full Text] [Related] [New Search]