This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Moy, B. C. Articles by Bhuyan, B. K. Search for Related Content PubMed PubMed Citation Articles by Moy, B. C. Articles by Bhuyan, B. K.

Interaction of CC-1065 and Its Analogues with Mouse DNA and Chromatin

Departments of Cancer and Infectious Diseases Research [B. C. M., B. K. B.], and Physical and Analytical Chemistry [M. D. P., W. C. K.], The Upjohn Company, Kalamazoo, Michigan 49001

CC-1065 is a potent antitumor antibiotic which is cytotoxic to P388 and L1210 leukemia cells in vitro and in vivo. CC-1065 covalently binds to calf thymus DNA preferentially to adenine-thymine regions at N3 of adenine. Here, we compare CC-1065 interaction with P388-derived chromatin, DNA, and histones as measured by electronic absorption and circular dichroism. Two CC-1065 analogues (U-71,184 and its enantiomer, U-71,185) which show different biological activities from CC-1065 were also studied.

The shape and temporal behavior of the induced circular dichroism curves generated by CC-1065 or its analogues bound to chromatin were similar to CC-1065 plus DNA. This suggested that CC-1065 and its analogues bind to the minor groove of chromatin DNA in a manner similar to calf thymus DNA. However, the binding of CC-1065 and its analogues to DNA induced a more intense circular dichroism band than binding to chromatin. The order of interaction for both chromatin and DNA was CC-1065>U-71,184>U-71,185. In contrast to the essentially irreversible binding to DNA after 24-h incubation, binding to chromatin was primarily a reversible interaction, the degree of reversibility being U-71,185>U-71,184 = CC-1065. CC-1065 binds weakly and nonspecifically to histones.

¹ Present acdress: Abbott Laboratories, 1400 Sheridan Road, Dept. of Clinical Immunology, North Chicago, IL 60064.

² To whom requests for reprints should be addressed, at Cancer and Infectious Diseases Research, The Upjohn Company, 301 Henrietta Street, Kalamazoo, MI 49001.

Received 7/20/88. Revised 12/ 1/88. Accepted 1/18/89.