8,9‐Dihydro‐8,9‐dihydroxybenz(a)anthracene 10,11‐oxide: A new type of polycyclic aromatic hydrocarbon metabolite

Purification of rat liver epoxide hydratase to apparent homogeneity

“…It has been reported [4,5] that dihydrodiols formed from some polycyclic hydrocarbons (benz(a)anthracene and benzo(a)pyrene) are reactivated by the microsomal monooxygenases to dihydrodiol epoxides which may represent ultimate carcinogens. If this is the case epoxide hydratase could play a critical role being responsible both for forming the proximate carcinogen and removing the ultimate carcinogen.…”

Transplacental control of epoxide hydratase and its relationship to the control of microsomal monooxygenase

“…Such alterations of important biomacromolecules can involve disturbancies of the ordered sequences and interrelationships of biochemical events in a cell in such a way as to lead to mutagenicity, carcinogenicity or cell necrosis (for a review see [l] ). In the subcellular compartment were these epoxides are formed, the endoplasmatic reticulum, they can be metabolized by epoxide hy.lratase(s) (EH) (EC 4.2.1.63) to much less reactive dihydrodiols (for a review see [2] ; for reactivation of a dihydrodiol by epoxidation at another site, and inactivation of the resulting mixed dihydrodiol-epoxide by epoxide hydratase-catalyzed transformation to a tetrahydrotetrol see [3,4]). Induction of EH would therefore be of great experimental and possibly practical interest, especially if MO responsible for the formation of epoxides, was not concomitantly induced.…”

Metabolism of benzo[a]pyrene: conversion of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene to highly mutagenic 7,8-diol-9,10-epoxides.

“…Borgen et al (9) found that the liver microsomal metabolism (11). The 8,9-dihydrodiol of benz [a]anthracene is also converted to a diol epoxide which binds to DNA (12) and is converted to a tetraol (13). BP (14), liver microsomes (15), and by a highly purified monoxygenase system containing cytochrome P-448 (16).…”