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Induction of Protein-DNA Complexes in HeLa S3 Cells by KW-2149, a New Derivative of Mitomycin C

Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Tokyo [N. F., H. N.]; Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka[H. A., H. S.]; and Sakai Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Osaka [M. K.], Japan

¹ To whom requests for reprints should be addressed, at Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., 3-6-6 Asahimachi, Machida, Tokyo 194, Japan.

KW-2149 is a new water-soluble analogue of mitomycin C which shows a broad spectrum antitumor activity in experimental tumor models including mitomycin C-resistant tumors and is less hematotoxic than mitomycin C. We have found that KW-2149 increases protein-DNA complexes in HeLa S3 cells using the potassium/sodium dodecyl sulfate precipitation method which recovers largely DNA bound covalently to protein but does not precipitate DNA bound noncovalently to proteins. In contrast, no increase of the protein-DNA complexes are shown in cells treated with mitomycin C. Thus, KW-2149 binds covalently with both DNA and protein, and this may mediate for KW-2149 the potent and characteristic antitumor activity compared with mitomycin C.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 7/16/93. Accepted 8/19/93.