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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Mutagenicity of some N- and O-acyl derivatives of N-hydroxy-2-aminofluorene in V79 Chinese hamster cells.

Mutagenicity of 4 N- and O-acyl derivatives of N-hydroxy-2-aminofluorene (acyl: acetyl or myristoyl residue) was examined in V79 Chinese hamster cells in the absence of a metabolic activation system. N-Myristoyloxy-N-acetyl-2-aminofluorene (N-MyO-AAF) was toxic and weakly mutagenic, inducing 8-azaguanine-resistant (AZAr) mutants in V79 Chinese hamster cells in a concentration-dependent fashion; while N-acetoxy-N-myristoyl-2-aminofluorene (N-AcO-MyAF) and N-myristoyloxy-N-myristoyl-2-aminofluorene (N-MyO-MyAF) were neither cytotoxic nor mutagenic. Under the same conditions, N-acetoxy-N-acetyl-2-aminofluorene (N-AcO-AAF) was highly toxic and mutagenic. Neither of the 2 N-myristoyloxy derivatives was mutagenic in Salmonella typhimurium. These esters have been reported to produce local tumours at the site of their injection in rats, bo be electrophilic towards methionine, and to induce unscheduled DNA synthesis in cultured human fibroblasts. In view of the fact that some of the esters were mutagenic in neither S. typhimurium nor V79 Chinese hamster cells, our findings emphasize the need for multiple short-term tests in predicting potential carcinogenic activity of chemicals.[1]


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