Free radicals in anticancer drug pharmacology.

This review examines the formation of free radical intermediates from a number of clinically active antitumor agents including quinone-containing antibiotics and etoposide. An attempt is also made to relate the formation of these reactive intermediates to biochemical and pharmacological basis for tumor cell kill and resistance. The formation of these intermediates in some tumor cells has been detected by both direct ESR and spin-trapping technique. The detection of free radicals in biological systems, however, depends upon cellular bioenvironments, e.g. reducing conditions, and the presence and/or absence of activation and detoxification mechanisms. Evidence shows that certain antitumor drugs generate free radicals in vitro and in vivo and that these reactive species kill tumor cells by causing damage to DNA, membranes or enzymes.