Activation and inactivation of neocarzinostatin-induced cleavage of DNA.

The possible role of free radicals in the mechanism of neocarzinostatin (NCS) action was studied. While mercaptene markedly stimulate the ability of NCS to degrade DNA, they also rapidly inactivate the antibiotic in a preincubation and at higher concentration inhibit the degradation reaction. The radiation protector S,2-aminoethylisothiuronium bromide-HBr is the most potent compound tested. Scavengers of diffusible OH radicals, O2- or H2O2 do not result in significant inhibition of the oxygen-dependent cleavage of DNA by NCS; in fact, alcohols and other organic solvents stimulate the reaction several-fold. By contrast, the potent peroxyl free radical scavenger, alpha-tocopherol, blocks the reaction 50% at 50 micron.