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 2- to 10-fold higher compared to those of normal thymus. Furthermore, mutant frequencies in the forward mutation assay of DNA synthesis were increased 2- to 7-fold in cell extracts from thymic lymphomas compared to those from normal thymus. As the DNA polymerase β (pol β) activity was extremely high in the thymic lymphomas, we screened mutations in the pol β gene to examine the possibility of involvement of mutated pol β in 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 β gene is not a major causal event.

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This work was supported by a grant from OB-GYN Akiyama Memorial Hospital, Hakodate, Japan, and Taiho Pharmaceutical Co., Ltd., Saitama, Japan.

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