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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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