METABOLISM OF POLYCYCLIC COMPOUNDS. THE METABOLISM OF 9,10-EPOXY-9,10-DIHYDROPHENANTHRENE IN RATS

Abstract

-9, 10-Epoxy-9, 10-dihydrophenanthrene is converted by rats into trans-9, 10-dihydro-9, 10-dihydroxyphenanthrene and its conjugates and into N-acetyl-S-(9, 10-dihydro-9-hydroxy-10-phenanthryl)-L-cysteine. Small amounts of 9-phenanthryl sulphate and glucosiduronate are also formed, together with 9-hydroxy-10-phenanthryl sulphate. The epoxide readily rearranges to 9-hydroxy- phenanthrene and reacts with water to give the dihydrodihydroxy compound and with N-acetylcysteine to give the mercapturic acid. One of the diastereoisomeric forms of the methyl ester of the mercapturic acid is identical with the ester of the mercapturic acid excreted by rats dosed with the epoxide or by rats and rabbits dosed with phenan-threne. A rat-liver homogenate converts the epoxide into trans-9, 10-dihydrodihydroxyphenanthrene and S-(9, 10-dihydro-9-hydroxy-10-phenanthryl)glutathione. The latter compound was not formed when boiled rat-liver homogenate was used, but was formed chemically from the epoxide and glutathione under more vigorous conditions. The results provide further indications that the metabolism of aromatic hydrocarbons involves the intermediary formation of epoxides.