Inhibitors of topoisomerase I constitute a novel family of antitumor agents. The 
camptothecin derivatives topotecan and irinotecan represent new weapons in our 
arsenal for battling human cancer. These two drugs act specifically at the level 
of the topoisomerase I-DNA complex and stimulate DNA cleavage. This mechanism of 
action is not restricted to the camptothecins. Numerous topoisomerase I poisons 
including DNA minor groove binders such as Hoechst 33258 and DNA intercalators 
such as benzophenanthridine alkaloids and indolocarbazole derivatives have been 
discovered and developed. Another important group of topoisomerase I inhibitors 
contains drugs which prevent or reverse topoisomerase I-DNA complex formation. 
Many of these topoisomerase I suppressors are natural products (beta-lapachone, 
diospyrin, topostatin, topostin, flavonoids) which are believed to interact 
directly with the enzyme. This review is concerned with the different families 
of topoisomerase I poisons and suppressors. Their origin, chemical nature and 
mechanism of action are presented. The relationships between drug binding to DNA 
and topoisomerase I inhibition are discussed.