Reference SummaryHorio Y, Mol Carcinog 1996 Dec;17(4):217-23
Title |
Ki-ras and p53 mutations are early and late events, respectively, in urethane-induced pulmonary carcinogenesis in A/J mice. |
Authors |
Horio Y; Chen A; Rice P; Roth JA; Malkinson AM; Schrump DS |
Journal |
Mol Carcinog |
Volume |
17 |
Issue |
4 |
Year |
1996 |
Pages |
217-23 |
Abstract |
In the A/J strain of mice, urethane (ethyl carbamate) induces lung hyperplasia, adenoma, and adenocarcinoma in a time-dependent manner. These distinct morphological stages may correlate with sequential molecular genetic changes in this mouse model. To test this hypothesis, we investigated the presence of mutations involving Ki-ras and p53 in urethane-induced lung lesions in A/J mice at early and late stages of tumorigenesis. We precisely microdissected 40 lung lesions from paraffin-embedded sections. Ki-ras mutations around codon 61 and p53 mutations in exons 5-8 were identified by polymerase chain reaction-single-strand conformation polymorphism and DNA sequencing techniques. In 29 early-stage lung lesions classified as hyperplasias (seven) or adenomas (22), we observed 19 Ki-ras mutations (66%), including three silent mutations and one double mutation at different codons, and one silent p53 mutation (3.5%). In 11 late-stage adenomas, we identified nine activating Ki-ras mutations (82%) and four missense p53 mutations (36%). These results indicate that Ki-ras mutations arise early, whereas p53 mutations occur relatively late during the benign stages of urethane- induced lung carcinogenesis in A/J mice. (C) 1996 Wiley- Liss, Inc. |
Links |
J:38027 – MGI References 8989915 – 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 hyperplasia |
|
Lung |
observed |