Metabolism of 2-methylnaphthalene to isomeric dihydrodiols by hepatic microsomes of rat and rainbow trout.

The metabolism of 2-methylnaphthalene in rats (in vivo and in vitro) and rainbow trout (in vitro) has been investigated. Three isomeric dihydrodiols were formed by microsomal preparations and these were isolated and identified by high-pressure liquid chromatography and gas chromatography/mass spectroscopy. The temperature, microsomal protein content, and incubation time were varied to obtain the optimum conditions for their formation. The conversion of 2-methylnaphthalene to both monohydroxylated compounds and dihydrodiols was reduced by incubation with carbon monoxide, the omission of NADPH, or use of heat-denatured microsomes, implying the involvement of cytochrome(s) P-450-linked mixed-function oxidase activity. The three dihydrodiols obtained in vitro in microsomes from both rat and fish were identical with those compounds isolated from rat urine. Pretreatment with phenobarbital and beta-naphthoflavone selectively altered the rate of formation of specific dihydrodiols by rat liver microsomes. Although phenobarbital had no significant effect on the rate of dihydrodiol formation in trout liver microsomes, beta-naphthoflavone was a strong inducer and its selectivity in increasing the rate of dihydrodiol formation was similar to that seen with rat liver microsomes.