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Differential regulation of two microsomal epoxide hydrolases in hyperplastic nodules from rat liver.

Two microsomal epoxide hydrolases of the rat liver were found to be differentially regulated in hyperplastic nodules. Whilst the activity for substrates of the well-known microsomal epoxide hydrolase with a broad substrate specificity (EHb), benzo[a]pyrene 4,5-oxide and androstene oxide (16 alpha, 17 alpha-epoxyandrosten-3-one), was greatly (approximately 5-fold) increased in the nodule microsomes and moderately (approximately 2-fold) increased in the surrounding tissue, that for the substrate of the novel microsomal epoxide hydrolase, cholesterol 5 alpha,6 alpha-oxide (EHch) remained unchanged. Since both enzymes convert endogenous steroid epoxides but with distinct structural features, this differential regulation may indicate a role of endogenous steroid epoxide(s) of a defined structure during hepatocarcinogenesis. Alternatively, this differential regulation may serve as a marker during hepatocarcinogenesis.