J. Weisburger, R. S. Yamamoto, G. Williams
Mar 1, 1972
Citations
1
Influential Citations
156
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Quality indicators
Journal
Cancer research
Abstract
Summary The problem of the biochemical activation steps required to elicit carcinogenicity to rat liver by N -2-fluorenylacetamide was investigated by bioassay, competitive inhibition, and biochemical techniques. Acetanilide inhibits not only the hepatocarcinogenicity of N -2-fluorenylacetamide but also that of the carcinogenic N -hydroxylated metabolite. With the parent compound, the inhibition was traced chiefly to competition at the N -hydroxylation step, which should not apply to the N -hydroxy derivative. With the latter, the addition of sodium sulfate to the diet restores the hepatocarcinogenicity of N -hydroxy- N -2-fluorenylacetamide in the presence of inhibitory acetanilide. However, sulfate addition fails to return carcinogenicity in the system N -2-fluorenylacetamide plus acetanilide, wherein the inhibition lies at the N -hydroxylation step. The combined results provide evidence that sulfate ester formation constitutes a required second activation step for the expression of carcinogenicity to the liver of rats of N -hydroxy- N -2-fluorenylacetamide, obtained by a first activation step. The required sulfotransferase enzyme system is found mainly in liver cytosol, but attempts to locate it in rat liver nuclear fractions resulted in the detection of only questionable amounts.