Mechanism of species difference in N-hydroxyphenacetin mutagenicity: The role of deacetylation by rat and hamster liver microsomes.

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Abstract
The mechanism of species difference in N-hydroxyphenacetin mutagenicity was investigated by using the Salmonella/microsome mutagenicity test and high-performance liquid chromatographic (HPLC) analysis. Mutagenicity of N-hydroxyphenacetin in Salmonella typhimurium TA100 was about 10 times more efficiently detected with a liver 9000g supernatant fraction (S9) from hamsters than with the corresponding fraction from rats in the absence of a reduced nicotinamide adenine dinucleotide phosphate-generating system. Paraoxon and sodium fluoride, both inhibitors of microsomal amidase, not only inhibited the mutagenicity of N-hydroxyphenacetin, but also retarded the formation of the deacetylation product, p-nitrosophenetole, a strong intrinsic mutagen. The N-hydroxyphenacetin-deacetylation activity was about 20 times higher in liver microsomes from the hamster than in those from the rat.