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Effect of an Epipodophyllotoxin Derivative (VP 16-213) on Macromolecular Synthesis and Mitosis in Mastocytoma Cells in Vitro¹

Biological and Medical Research Division, Sandoz Ltd., CH-4002 Basel, Switzerland

The influence of the semisynthetic epipodophyllotoxin derivative VP 16-213 on different cellular and biochemical parameters was determined with the use of suspension cultures of a murine mastocytoma. Cells were exponentially dividing and not synchronized. Treatment with VP 16-213 (1 µg/ml) reduced the mitotic index by more than 75% within 1.5 hr and completely prevented cell multiplication upon further incubation. DNA, RNA, and protein content per cell showed an increase upon treatment with 1 or 10 µg/ml. Thymidine incorporation, on the other hand, was reduced by 60 and 80% when P-815 cells were treated for 6.5 hr with 1 or 10 µg of the drug per ml. Incorporation of uridine and leucine into RNA and protein was enhanced with the drug (1 µg/ml), while with 10 µg/ml, uridine incorporation was reduced. These results show that precursor incorporation studies are not necessarily reflecting the synthesis of these macromolecules and suggest that VP 16-213 arrests cells in late S or G₂ phase of the cell cycle.

¹ A preliminary report of this work was presented at the Fifth Annual Meeting of the Swiss Society of Experimental Biology, May 1973 (7).

² To whom reprint requests should be addressed.

Received 11/19/73. Accepted 2/ 4/74.