DNA-DNA interstrand cross-linking by FR66979 and FR900482: Requirement of metal ions during reductive activation

✍ Scribed by Manuel M. Paz; Paul B. Hopkins

• Book ID: 104256094
• Publisher: Elsevier Science
• Year: 1997
• Tongue: French
• Weight: 315 KB
• Volume: 38
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(96)02347-7

✦ Synopsis

The antitumor antibiotics FR66979 and FR900482 are believed to undergo bioreductive activation in vivo, enabling them to alkylate DNA. Reduction has previously been accomplished in vitro using sodium dithionite or dithiothreitol. We find that metal ions are a previously unrecognized, critical component of these reactions, which are suppressed by addition of EDTA and greatly stimulated by addition of catalytic quantities of iron(ll) salts. This finding should greatly facilitate the elucidation of the details of the reaction cascades which follow reductive activation.