The effect of ammonium sulfate on the metabolism of dimethylnitrosamine and other xenobiotics by rat hepatic microsomes.
The addition of 125--1000 mM (NH4)2SO4 to rat hepatic washed microsomal preparations was found to stimulate markedly the rate of in vitro metabolism of the hepatocarcinogen dimethylnitrosamine. Solute treatment also stimulated the activities of NADPH-cytochrome c reductase, NADPH oxidase, the N-oxidation of N,N-dimethylaniline, and the fluorescent interaction of 8-anilino-1-naphthalenesulfonic acid (ANS) with hepatic microsomes. (NH4)2SO4 had a varied effect on the activities of a number of mixed-function oxidase (MFO) enzyme activities. Whereas the activities of aniline 4-hydroxylase and 4-nitrobenzoic acid nitroreductase were enhanced at all solute concentrations, several other MFO enzyme activities were either progressively inhibited or stimulated at low and inhibited at high (NH4)2SO4 concentrations. Solute treatment had no effect on microsomal cytochrome P-450 content but inhibited the activities of glucose 6-phosphatase and UDP-glucuronyltransferase. All of the observed changes in enzyme activities and ANS-microsome fluorescence interaction were found to be reversible when the solute was removed by centrifugation. These findings suggest that (NH4)2SO4 and certain other solutes can reversibly modify the conformation of microsomal membranes in such a manner as to affect microsomal enzyme activities.