Comparative metabolism and excretion of benzo(a)pyrene in 2 species of ictalurid catfish

Differential susceptibility of polycyclic aromatic hydrocarbon (PAH)-mediat ed liver cancer exists in two related species of Icta-lurid catfish. Two hy potheses are addressed in this study to explain this difference. Specifical ly, the relatively insensitive channel catfish 1) do not produce mutagenic PAH metabolites, and/or 2) they more quickly eliminate PAHs due to greater Phase II enzyme activities than the more sensitive brown bullhead. Livers a nd bile were collected from each species 6, 24, 72, and 168 h after a singl e 10 mg/kg i.p. benzo(a)pyrene (BaP) exposure, BaP treatment had no signifi cant effect on cytosolic 1-chloro-2,4-dinitrobenzene or ethacrynic acid (EA )-glutathione-S- transferase (GST) and cis-stilbene oxide-microsomal epoxid e hydrolase (EH) activities of either species. Channel catfish EH and GST a ctivities were 1.2-fold higher than brown bullhead activities (p = 0.058 an d p < 0.002, respectively). HPLC-APCI-MS of extracted bile and bile enzymat ically digested to detect glucuronyl transferase (GT), GST, and sulfotransf erase (ST) conjugated metabolites indicated no species differences in elimi nation or profiles of total biliary metabolites. GT conjugates predominated ; ST and GST conjugates were minimal, BaP-diones accounted for the majority of metabolites in both species. Overall, these results indicated that brow n bullhead preferentially formed BaP-7,8-dihydrodiol, a precursor to the DN A-reactive BaP-7,8-dihydrodiol-9,10-epoxide (BPDE), which may be linked to the increased PAH susceptibility in this species.