Inter-species comparison of liver and small intestinal microsomal metabolism of fluoranthene

Abstract

The magnitude of susceptibility to toxicant exposure may depend on the ability of animals to metabolize the chemicals. The present study has been undertaken to see whether any differences exist among mammals in the metabolism of fluoranthene (FLA), a polycyclic aromatic hydrocarbon (PAH) compound. Microsomes were isolated from the small intestine and liver of rat, mouse, hamster, goat, sheep, pig, dog, cow, monkey, and humans (commercially procured), and incubated with FLA. Post-incubation, samples were extracted with ethyl acetate and analyzed for FLA/metabolites by reverse-phase HPLC with fluorescence detection. The metabolism of FLA in both liver and small intestine was in the order: human > monkey > cow > goat > sheep > dog > pig > hamster > rat > mouse under conditions of the test system used. The rate of metabolism (pmol of metabolite/min/mg protein) was found to be more in liver than in intestine in all the species studied. The FLA metabolites identified were FLA 2,3-diol, trans-2,3-dihydroxy-1,10b-epoxy-1,2,3,10β tetrahydro FLA (2,3D FLA), 3-hydroxy FLA, and 8-hydroxy FLA. The rodent microsomes produced considerably higher proportion of FLA 2,3-diol, and 2,3D FLA than did pig, dog, and humans. On the other hand, microsomes from higher mammals converted a greater proportion of FLA to 3-hydroxy FLA, the detoxification product of FLA. Overall, our results revealed a great variation among species to metabolize FLA.