Chemically Induced Primary Thymic Lymphomas of Mice Reduced Fidelity of DNA Synthesis in Cell Extracts from Updated Version

To examine whether the fidelity of DNA synthesis is reduced in tumor cells, M13 mp2-based fidelity assays were carried out using 15 samples of whole-cell extracts from primary mouse thymic lymphomas induced by alkylating agents. We found that DNA synthesis activities of thymic lymphomas, detected as incorporation of [3H]TTP into acid-insoluble materials, were 2to 10-fold higher compared to those of normal thymus. Furthermore, mutant frequencies in the forward mutation assay of DNA synthesis were increased 2to 7-fold in cell extracts from thymic lympho mas compared to those from normal thymus. As the DNA polymerase /! (pol ß) activity was extremely high in the thymic lymphomas, we screened mutations in the pol ßgene to examine the possibility of involvement of mutated pol ßin reduction of the fidelity of DNA synthesis. Of 20 lymphomas, one case of point mutation (T to A) was found by reverse transcription-PCR single-strand conformation polymorphism analysis. These results suggest that the mutagenic DNA synthesis is involved in murine thymic lymphoma genesis, although mutation of the pol ßgene is not a major causal event.