Metabolism of polycyclic compounds. 23. The metabolism of pyrene in rats and rabbits

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Abstract
The H2SO4 acid and glucuronic acid conjugates of l-hydroxypyrene, 1,6- and 1,8-dihydraxypyrene and trans-4,5-dihydro-4, 5-dihydroxypyrene, together with N-acetyl-S-(4,5-dihy-dro-4-hydroxy-5-pyrenyl)-L-cysteine, were found in the urine of both rats and rabbits treated with pyrene. Two compounds giving rise to pyrene with mineral acid were also detected, but neither 4-hydrcocy-pyrene nor its conjugates was present. N-Acetyl-S-(4,5-dihydroxy-5-pyrenyl)-L-cysteine and the corresponding cysteine, cysteinylglycine and glutathione derivatives, as well as glucuronic acid conjugates of 1-hydroxypyrene and trans-4,5-dihydro-4,5-dihydraxypyrene, were present in the bile of rats treated with pyrene. In the oxidation of pyrene with perbenzoic acid an intermediate was formed, believed to be 4,5-epoxy-4,5-dihydropyrene, which reacted with water to yield trans-4,5-dihydro-4,5-dihydroxypyrene and with N-acetyl-L-cysteine to form N-acetyl-S-(4,5-dihydro-4-hydroxy-5-pyrenyl)-L-cysteine. l-Hydroxypyrene and 1,6- and 1,8-pyrenequinone were also formed in the oxidation. The N-acetylcysteine derivative obtained both synthetically and from treated animals yielded pyrene and NN''-diacetylcystine and a compound believed to be 4-pyrenylmercapturic acid with mineral acid and 4-hydroxypyrene with aqueous alkali.