Effect of benzene on hepatic drug metabolism and ultrastructure

Benzene metabolism was stimulated in rat liver microsomes after treatment of rats with benzene but not after treatment with phenol or resorcinol. Pretreatment of rats with hydroquinone, pyrocatechol and pyrogallol inhibited benzene metabolism in vitro. Single large doses of benzene also stimulated the metabolism of zoxazolamine, neoprontosil and p-nitrobenzoic acid but not that of hexobarbital or chlorpromazine. During the course of daily benzene treatments, the metabolism of zoxazolamine was stimulated after 7 days, while 14 days of treatment was necessary for benzene and neoprontosil. The metabolism of hexobarbital and p-nitrobenzoic acid was inhibited after 14 days. Electron microscopic studies of the liver showed proliferation of the smooth endoplasmic reticulum (SER) after 7 and 14 days of benzene treatment. It is concluded that benzene, not its hydroxylated derivatives, is probably responsible for benzene-induced microsomal stimulation and that benzene-induced proliferation of SER does not ensure an increase of the metabolism of all drugs.