Comparative metabolism and excretion of benzo(a)pyrene in 2 species of ictalurid catfish.
Differential susceptibility of polycyclic aromatic hydrocarbon (PAH)-mediated liver cancer exists in two related species of Ictalurid catfish. Two hypotheses are addressed in this study to explain this difference. Specifically, 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 and bile were collected from each species 6, 24, 72, and 168 h after a single 10 mg/kg i.p. benzo(a)pyrene (BaP) exposure. BaP treatment had no significant effect on cytosolic 1-chloro-2,4-dinitrobenzene or ethacrynic acid (EA)-glutathione-S:- transferase (GST) and cis-stilbene oxide-microsomal epoxide hydrolase (EH) activities of either species. Channel catfish EH and GST activities were 1.2-fold higher than brown bullhead activities (p = 0.058 and p < 0.002, respectively). HPLC-APCI-MS of extracted bile and bile enzymatically digested to detect glucuronyl transferase (GT), GST, and sulfotransferase (ST) conjugated metabolites indicated no species differences in elimination 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 brown bullhead preferentially formed BaP-7,8-dihydrodiol, a precursor to the DNA-reactive BaP-7, 8-dihydrodiol-9,10-epoxide (BPDE), which may be linked to the increased PAH susceptibility in this species.
Willett
K L
KL
Ecotoxicology Laboratory, Nicholas School of the Environment, Duke University, Durham, North Carolina 27708-0328, USA. Kwillett@olemiss.edu
Gardinali
P R
PR
Lienesch
L A
LA
Di Giulio
R T
RT
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism* / Q000633:toxicity; D001646:Bile / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism* / Q000633:toxicity; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000187:drug effects; D018736:DNA Adducts / Q000187:drug effects; D004137:Dinitrochlorobenzene / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000378:metabolism; D004976:Ethacrynic Acid / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007059:Ictaluridae / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D013045:Species Specificity
D002273:Carcinogens; D018736:DNA Adducts; D004137:Dinitrochlorobenzene; D001564:Benzo(a)pyrene; D004247:DNA; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; C048095:stilbene oxide hydrolase; D004976:Ethacrynic Acid