EFFECT OF NITROHETEROCYCLIC DRUGS ON DNA - INVITRO MODEL OF CYTOTOXICITY

Electrolytic reduction of several nitroheterocyclic drugs was carried out at controlled potentials under anoxic (anaerobic) conditions in the presence of Esherichia coli DNA. The DNA was examined during the reduction process by viscometry, determination of Tm values, and thermal renaturation of DNA; its single strand content was determined using hydroxyapatite chromatography and its electrophoretic migration characteristics in acridine-impregnated agarose gels. All the drugs examined decreased the viscosity, thermal renaturation and Tm value, and increased the single strand content and migration distance of DNA. The results indicate that the drugs cause strand breakage of DNA as a primary mechanism of action, resulting in extensive loss of helix formation and a concomitant decrease in molecular weight. The method of drug reduction and the techniques to assess DNA damage may be used as a model to determine the relative cytotoxicities and the potential of such agents as antimicrobial and radiosensitizing drugs. © 1979.