Consistent Oncogene Methylation Changes in Epithelial Cells Chemically Transformed In vitro

摘要

Many cancers occurring in humans and in animals are accompanied by alterations in oncogene DNA sequences, amplification, or changes in expression. In some cases the changes are quite specific and prevalent such as in Burkitt's lymphoma, pancreatic, and thyroid carcinoma. Studies of human lung cancers have revealed heterogeneous activated oncogenes in varied proportions of tumors and prompted researchers to consider that genetic events present in established tumors may not be reflective of those occurring early in precursor initiated cells. The rat tracheal epithelial (RTE) cell transformation system has been utilized as a surrogate to study early molecular events in respiratory carcinogenesis. RTE cells transformed by chemical carcinogens in vitro and early preneoplastic lesions in vivo have been examined. However, RTE cells transformed by polycyclic hydrocarbons appear to sustain no consistent changes in Ha-ras, c-myc, and Ki-ras oncogenes by restriction fragment length polymorphism analysis, and DNA isolated from these cells is devoid of transfectable transforming genes in NIH3T3 cells. In the present study it has been determined that rat tracheal epithelial cells transformed by diverse carcinogens share common changes in DNA methylation patterns in Ha-ras and c-myc oncogenes as determined by Hpa II digestion. This is the first report of a common molecular alteration for these cells.