Reference SummaryYou M, Carcinogenesis 1992 Sep;13(9):1583-6
Title |
Mutagenesis of the K-ras protooncogene in mouse lung tumors induced by N-ethyl-N-nitrosourea or N-nitrosodiethylamine. |
Authors |
You M; Wang Y; Lineen AM; Gunning WT; Stoner GD; Anderson MW |
Journal |
Carcinogenesis |
Volume |
13 |
Issue |
9 |
Year |
1992 |
Pages |
1583-6 |
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. |
Links |
J:70504 – MGI References 1394843 – National Library of Medicine/PubMed |
Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
---|---|---|---|---|---|
A/J | Lung adenoma |
|
Lung |
observed |
|
A/J | Lung adenoma |
|
Lung |
observed |
|
A/J | Lung tumor | Lung |
observed |