Genetic and physiological modulation of anthracycline‐induced mutagenesis in Salmonella typhimurium

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Abstract
The genotoxic properties of adriamycin and daunomycin, anthracycline antibiotics effective in the treatment of a wide variety of malignancies, were examined in the Salmonella/Ames reverse‐mutation test. A novel time‐ and temperature‐dependent phenomenon that potentiates the mutagenicity of these compounds, termed mutational enhancement, is described. The results of congeneric and chemical attenuation studies imply that anthracycline‐induced free radicals contribute substantively to the mutagenic potentials of adriamycin and daunomycin. These studies show that adriamycin and daunomycin are not simple intercalative compounds. Rather, anthracycline‐induced mutagenesis entails at least two separate but intimately related steps, namely, intercalation within discrete base sequences and the free‐radical‐mediated events that ensue. Implications of the nonrandom and site‐specific action of the anthracyclines are discussed.