Prostaglandin D2 lowers nuclear DNA polymerase activity in cultured mastocytoma cells |
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Authors: | Mieko Kawamura Yasuko Koshihara |
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Affiliation: | Department of Pharmacology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo-173, Japan |
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Abstract: | Prostaglandin D2 strongly inhibited growth of cultured mastocytoma P-815, 2-E-6 cells, which were established and cloned from mouse mast tumor cells. The inhibition was dose-dependent (IC50 = 2.09 × 10−5 M). Prostaglandin D2 also inhibited the DNA synthesizing activity of the cells dose-dependently. We next measured the activities of endogenous DNA polymerases extracted from untreated and prostaglandin D2-treated cells. Prostaglandin D2 pretreatment reduced DNA polymerase α activity by 52%. The sedimentation coefficients of the enzymes from untreated and prostaglandin D2-treated cells were the same suggesting there was no gross change in the size of the enzyme. Prostaglandin D2 pretreatment of the cells reduced endogenous DNA polymerase β activity to 68% of the control value; the sedimentation coefficients of the enzymes from treated and untreated cells were both 3.5 S. Interestingly, prostaglandin D2 had no direct inhibitory effect on the activity of either DNA polymerase α or β. Our results indicate that the activities of DNA polymerase α and β are lower in prostaglandin D2-treated mastocytoma cells. This finding account for the lower level of DNA synthesis in these cells. |
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Keywords: | To whom reprint request should be addressed |
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