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- W1975878493 abstract "Summary Hycanthone methanesulfonate-a highly efficacious antischistosomal drug—has previously been shown to induce forward mutations at the thymidine kinase (TK) locus in cultured L5178Y mouse lymphoma heterozygote (TK +/− ) cells. It is also mutagenic in microorganisms, in Drosophila, and in rats but not in mice. In this study a number of structural analogs of hycanthone have been examined in the TK heterozygote system in order to relate structural modifications to mutagenic and toxic events. Mutagenicity as a function of molar concentration varies extensively and sometimes in a quite complex manner among the analogs tested. Thus, to cite extremes, the 6-chloro indazole derivative of lucanthone, IA-3, is nearly non-mutagenic at concentrations resulting in up to 90% inhibition of growth, while the corresponding des-chloro indazole derivative, IA-5, is between 10- and 100-fold more mutagenic than IA-3. Further, the dose-mutagenic response curves of IA-5, IA-6 (the des-chloro indazole derivative of hycanthone) and, to a lesser extent, of lucanthone and hycanthone exhibit at low concentrations a dose-dependent increase in mutagenicity, peaking at 20–50 μ M ; this portion of the curve is followed by an intermediate concentration range over which mutagenic response decreases with increasing concentration. Finally, at high concentrations the mutagenic response again increases with concentration or levels off. These complex mutagenic responses are mirrored by the dose-toxicity curves which show a minimum survival at concentrations yielding mutagenicity maxima and increased survivals where mutagenicity is low." @default.
- W1975878493 created "2016-06-24" @default.
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- W1975878493 date "1974-08-01" @default.
- W1975878493 modified "2023-09-29" @default.
- W1975878493 title "Mutagenicity of thioxanthenes (hycanthone, lucanthone and four indazole derivatives) at the TK locus in cultured mammalian cells" @default.
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- W1975878493 doi "https://doi.org/10.1016/s0027-5107(74)80028-x" @default.
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