Changes in rat liver microsomal cytochrome P-450 and enzymatic activities after the inhalation of n-hexane, xylene, methyl ethyl ketone and methylchloroform for four weeks

Abstract

Groups of Sprague-Dawley rats were exposed, by inhalation, to n-hexane (900 ppm, 3.240 mg/m3), xylene (600 ppm, 2.625 mg/m3), methyl ethyl ketone (800 ppm, 2.345 mg/m3) and methylchloroform (800 ppm, 4.345 mg/m3) for four weeks. Increased liver weights and liver to body weight ratios were observed for all the solvents except n-hexane. An increased in vitro formation of certain metabolites of all the investigated substrates was found only in the rats exposed to xylene. The in vitro microsomal metabolism of biphenyl, benzo(a)pyrene, 4-androstene-3,17-dione and 5α-androstane-3α,17β-diol in combination with sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that n-hexane was without effect on rat liver microsomal cytochrome P-450 and that methyl ethyl ketone and methylchloroform depressed the formation of two metabolites of androstenedione but did not alter the concentration of cytochrome P-450 under the experimental conditions used. Xylene was shown to be a phenobarbital-like inducer of rat liver microsomal cytochrome P-450.