THE INHIBITION OF SOS-RESPONSES AND MDR BY PHENOTHIAZINE-METAL COMPLEXES

The gene of multidrug resistance (mdr) is inducible by different envir onmental stresses (SOS gene). We tested the inhibitory-action of some new metal complexes of phenothiazines on megacin encoding bacterial ge ne induced by mitomycin-C as an example of ''SOS induction'' and on ef flux pump of mouse lymphoma cells. The interaction of compounds to DNA was measured by thermal stability of DNA. It was found that metal co- ordination complexes of trifluoperazine (TFP) and chlorpromazine (CPZ) added before mitomycin administration have an inhibitory action on me gacine induction. The TFP-V(IV) complex was effective at a lower conce ntration than TFP alone. The inhibitory effect of some metal coordinat ing complexes (TFP-Cu(II) and TFP-V(IV)) exceeded the action of TFP al one on efflux pumps. We propose that these compounds can form a comple x with the regulatory protein or DNA resulting in the inhibition of SO S response and inhibit the mdr function by inactivating the P-glycopro tein as well.