Effects of Xylene and Xylene Isomers on Cytochrome P-450 and in Vitro Enzymatic Activities in Rat Liver, Kidney and Lung

Rats were exposed for 3 days by inhalation to 2000 ppm of a xylene mixture, or the individual constituents, o-xylene, m-xylene, p-xylene and ethylbenzene. All solvents increased hepatic cytochrome P-450 concentrations and NADPH-cytochrome c reductase activity, although p-xylene did not increase the cytochrome P-450 content as much as the other compounds, showing the importance of the substitution pattern. Increases were observed in the in vitro O-deethylation of 7-ethoxyresorufin and in the hydroxylation of n-hexane and benzo[a]pyrene. The metabolite profiles obtained with these substrates and the results of gel electrophoresis in the presence of sodium dodecyl sulfate indicate that the induction is of the phenobarbital type. In kidney microsomes an increased concentration of cytochrome P-450 was obtained following exposure to a xylene mixture or to o- or m-xylene. The O-deethylation of 7-ethoxyresorufin was increased by exposure to all solvents. In lung microsomes xylene and xylene isomers but not ethylbenzene caused a decrease in cytochrome P-450 content and a reduction in n-hexane hydroxylation. However, the O-deethylation of 7-ethoxyresorufin was not affected. In general the effect of the xylene mixture reflected the content of the dominating component m-xylene. The ability of xylene and xylene isomers to modify the metabolism of other potentially toxic substances in liver, kidney and lung microsomes suggests the possibility of synergistic toxic responses.