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Reduced Fidelity of DNA Synthesis in Cell Extracts from Chemically Induced Primary Thymic Lymphomas of Mice¹

Department of Cell Genetics, Sasaki Institute, 2-2, Kanda-Surugadai, Chiyoda-ku, Tokyo 101 [Y. K., T. O.]; Department of Biology, Ochanomizu University, 2-1-1, Ohtsuka, Bunkyo-ku, Tokyo 112 [K. M-M.]; and Department of Physiology and Pathology, National Institute of Radiological Science, 4-9-1, Anagawa, Inage-ku, Chiba-shi, Chiba 263 [Y. S., T. O.], Japan

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 ß (pol ß) activity was extremely high in the thymic lymphomas, we screened mutations in the pol ß gene to examine the possibility of involvement of mutated pol ß 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 ß gene is not a major causal event.

¹ This work was supported by a grant from OB-GYN Akiyama Memorial Hospital, Hakodate, Japan, and Taiho Pharmaceutical Co., Ltd., Saitama, Japan.

² To whom requests for reprints should be addressed, at Imperial Cancer Research Fund, Clare Hall Laboratories, Blanche Lane, South Mimms, Potters Bar, Herts EN6 3LD, United Kingdom.

Received 4/17/95. Accepted 7/ 6/95.

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