Tissue and subcellular distribution of 3H-dioxane in the rat and apparent lack of microsome-catalyzed covalent binding in the target tissue

Using ³H-dioxane, the distribution of dioxane among a number of tissues and various subcellular fractions of rat liver was studied. At various times after i.p. injection, dioxane was found to distribute more or less uniformly among various tissues (liver, kidney, spleen, lung, colon and skeletal muscle), consistent with its polar/nonpolar nature. Studies of the nature of dioxane binding, however, revealed that the extent of “covalent” binding (as measured by incorporation into lipid-free, acid-insoluble tissue residues) was significantly higher in the liver (the main carcinogenesis target tissue), spleen and colon than that in other tissues. Investigations of the subcellular distribution in liver indicated that most of the radioactivity was in the cytosol, followed by the microsomal, mitochondrial and nuclear fractions. The binding of dioxane to the macromolecules in the cytosol was mainly noncovalent. The percent covalent binding was highest in the nuclear fraction, followed by mitochondrial and microsomal fractions and the whole homogenate. Pretreatment of rats with inducers of microsomal mixed-function oxidases had no significant effect on the covalent binding of dioxane to the various subcellular fractions of the liver. There was no microsome-catalyzed $\text{in}$$\text{vitro}$ binding of ³H- or ¹⁴C-dioxane to DNA under conditions which brought about substantial binding of ³H-benzoa]pyrene.