Mutagenic and cytotoxic potencies of a series of anthracycline derivatives as measured by HIS+ reversion, 8-azaguanine resistance and direct plating cytotoxicity tests inSalmonella typhimurium

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Abstract
His+ reversion at multiple his− loci, 8‐azaguanine resistance, and a previously reported direct plating cytotoxicity test were used to measure the genotoxic potencies of a series of anthracycline derivatives in Salmonella typhimurium. N‐demethylated amino sugar monosaccharide anthracyclines reverted most his−tester strains and were positive with 8‐azaguanine selection. Reversion of strain TA98 was the most sensitive end point for measuring the mutagenic activity of the N‐demethylated anthracyclines. N,N‐dimethyl amino sugar derivatives of Adriamycin and daunomycin were negative as measured by His+ reversion in tester strain TA98, but generated positive responses in tester strain TA102 that were equal to or greater than those of the demethylated parent coumpounds. Similarly, N,N‐dimethyl amino sugar derivatives of pyrromycinone and 1‐deoxypyrromycinone had no mutagenic activity as measured by His+ reversion except in tester strains TA102 and TA104. These later compounds also gave positive responses with 8‐azaguanine selection. In view of these results, the importance of amino sugar dialkylation and anthracycline mechanisms of mutagenesis are discussed.