EFFECTS OF ANTIMUTAGENS ON DEVELOPMENT OF DRUG ANTIBIOTIC RESISTANCE IN MICROORGANISMS/

The effects of polyamines and related compounds on the development of drug/antibiotic resistance in a variety of bacterial strains were stud ied. Methods employed included standard toxicity assays, modified Ames tests for mutation frequencies and antimutagenic effects, prophage in duction assays, and recA-lacZ and ada-lacZ induction assays. Using the se methods, we have shown that the polyamines produce strong antimutag enic effects against EMS and MMS-induced antibiotic resistance. Spermi dine also seems to have antimutagenic potential against 4NQO-induced m utations. DNA fidelity assays suggest that polyamines play a vital rol e in DNA synthesis, and several polyamines prevent the development of resistance to dihydrostreptomycin. The polyamine putrescine appears to be required for streptomycin action and also enhances the activity of some antibiotics (e.g., neomycin, kanamycin) but shows no enhancing e ffect on tetracycline or erythromycin. The potential significance of t hese studies for infectious diseases and tumor therapy is discussed. ( C) 1998 Elsevier Science B.V. All rights reserved.