Metastatic tumor burden in the lung of C57BL/6 or BDF1 mice was quantitated by measuring DNA polymerase a activity in the lung of tumor-bearing animals. DNA polymerase activity in the lung increased time-dependently following the inoculation of Lewis lung carcinoma (s.c.) or B16 melanoma variant B16–B2 (i.v.). In the Lewis lung carcinoma system, the number of metastatic modules and the weight of lung also increased time-dependently. Results from the B16 melanoma showed that the increase in lung nodules occurred 10 to 20 days after i.v. inoculation of tumor cells. DNA polymerase activity increased significantly during this period. Because the lung nodules were very small there was no obvious concomitant increase in lung weight. Since no significant infiltration of host cells was observed in the lung in response to metastatic foci, the rise in DNA polymerase activity should be due to tumor cells and not to infiltrating host cells. When the metastasis of Lewis lung carcinoma was inhibited by adriamycin and cyclophosphamide, decrease in DNA polymerase activity in the lung occurred. These results indicate that the degree of tumor metastasis can be quantitated by measuring DNA polymerase activity.
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Arens, M., Yamashita, T., Padmanabhan, R., Tsuruo, T., and Green, M., 1977, Adenovirus deoxyribonucleic acid replication. Characterization of the enzyme activities of a soluble replication system. Journal of Biological Chemistry, 252, 7947–7954.
Fidler, I. J., 1970, Metastasis: Quantitative analysis of distribution and fate of tumor emboli labelled with 125I-5-iodo-2′-deoxyuridine. Journal of National Cancer Institute, 45, 773–782.
Fidler, I. J., 1978, General considerations for studies of experimental cancer metastasis. Methods in Cancer Research, Vol. XV, edited by H. Busch (New York: Academic Press), pp. 399–439.
Karrer, K., Humphreys, S. R., and Goldin, A., 1967, An experimental model for studying factors which influence metastasis of malignant tumors. International Journal of Cancer, 2, 213–223.
Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Landall, R. J., 1951, Protein measurement with folin phenol reagent. Journal of Biological Chemistry, 193, 265–275.
Raz, A., and Hart, I. R., 1980, Murine melanoma. A model for intracranial metastasis. British Journal of Cancer, 42, 331–341.
Tsuruo, T., and Fidler, I. J., 1981, Differences in drug sensitivity among tumor cells from parental tumor, selected variants, and spontaneous metastasis. Cancer Research, 41, 3058–3064.
Tsuruo, T., Hirayama, K., and Ukita, T., 1975, Three DNA polymerase of rat ascites hepatoma cells: Properties of the enzymes and effects of RNA synthesis on the reaction. Biochemica et Biophysica Acta, 383, 274–281.
Tsuruo, T., Iida, H., Tsukagoshi, S., and Sakurai, Y., 1980, Growth inhibition of Lewis lung carcinoma by an inorganic dye ruthenium red. Gann, 71, 151–154.
Tsuruo, T., and Ukita, T., 1974, Purification and further characterization of three DNA polymerases of rat ascites hepatoma cells. Biochemica et Biophysica Acta, 353, 146–159.
Wexler, H., 1966, Accurate identification of experimental pulmonary metastases. Journal of National Cancer Institute, 36, 641–645.
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Tsuruo, T., Iida, H., Tsukagoshi, S. et al. Quantitative estimation of tumor metastasis by measurement of DNA polymerse activity. Clin Exp Metast 1, 39–49 (1983). https://doi.org/10.1007/BF00118471
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DOI: https://doi.org/10.1007/BF00118471