Ki-ras and p53 mutations are early and late events, respectively, in urethane-induced pulmonary carcinogenesis in A/J mice

Publisher Website
Google Scholar
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.

This publication has 27 references indexed in Scilit: