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[Cancer Research 50, 5841-5844, September 15, 1990]
© 1990 American Association for Cancer Research

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Induction of Mammalian DNA Topoisomerase II Dependent DNA Cleavage by Antitumor Antibiotic Streptonigrin

Yoshinori Yamashita1, Sho-zou Kawada, Noboru Fujii and Hirofumi Nakano

Tokyo Research Laboratories, Kyowa Hakko Kogyo Co. Ltd., 3-6-6 Asahimachi, Machida, Tokyo 194, Japan

Streptonigrin, a nonintercalative antitumor antibiotic, induced mammalian topoisomerase II dependent DNA cleavage in vitro. The cleavage activity of streptonigrin was comparable to that of demethylepipodophyllotoxin ethylidene-ß-D-glucoside at a low concentration (≤10 µM) but one-third lower at a higher concentration (>250µM). Exposure of a reaction mixture containing streptonigrin, DNA, and topoisomerase II to an elevated temperature (65°C) resulted in substantial reduction in DNA cleavage, suggesting that the mechanism of the topoisomerase II dependent DNA cleavage induced by streptonigrin was through the formation of a cleavable complex previously reported for topoisomerase II poisons such as 4'-(9-acridinylamino) methanesulfon-m-anisidide and epipodophyllotoxins.

1 To whom requests for reprints should be addressed.

Received 11/ 6/89. Accepted 6/13/90.




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N. Fujii, Y. Yamashita, T. Mizukami, and H. Nakano
Correlation between the Formation of Cleavable Complex with Topoisomerase I and Growth-Inhibitory Activity for Saintopin-Type Antibiotics
Mol. Pharmacol., February 1, 1997; 51(2): 269 - 276.
[Abstract] [Full Text] [PDF]




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Copyright © 1990 by the American Association for Cancer Research.