Southern flounder hepatic and intestinal metabolism and DNA binding of benzo[a]pyrene (BaP) metabolites following dietary administration of low doses of BaP, BaP-7,8-dihydrodiol or a BaP metabolite mixture.
Certain finfish species living in chemically polluted environments exhibit a high incidence of gastrointestinal tract tumors. Carnivorous fish in such environments are likely to consume invertebrates which contain chemical procarcinogens and the invertebrate biotransformation products of these compounds. The retention in tissues, extent of DNA adduct formation in liver and intestine, and metabolite composition of bile was investigated in southern flounder following gavage with pure [3H]- or [14C]benzo[a]pyrene (BaP), pure [14C]benzo[a]pyrene-7,8-dihydrodiol (BaP-7,8D), or hepatopancreas from spiny lobsters previously dosed with [3H]- or [14C]BaP (Metab.HP). Metab.HP contained mainly polar conjugates of BaP diols, triols and tetraols. BaP-7,8D was retained in fish tissues and bile at 24 h to a greater extent (33.6% of the dose), than either BaP (19.00%) or Metab.HP (6.6%). Hepatic and intestinal DNA isolated from all dosed fish contained covalently bound radioactivity, but exposure to BaP-7,8D or BaP resulted in significantly higher binding in both tissues than exposure to Metab.HP. Hepatic DNA from BaP and BaP-7,8D-dosed flounder contained 0.24 +/- 0.07 and 0.33 +/- 0.06 pmol BaP equivalents/mg DNA respectively (mean +/- S.E.), while hepatic DNA isolated from Metab.HP-dosed flounder contained 0.006 +/- 0.002 pmol BaP equivalents/mg DNA. Binding of radioactivity to intestinal DNA was significantly higher than to hepatic DNA for flounder dosed with Metab.HP (0.026 +/- 0.003) or with BaP (0.76 +/- 0.27) but not for flounder dosed with BaP-7,8D (0.44 +/- 0.09). These studies show that dietary BaP, and metabolites likely to be present in invertebrates, can be absorbed by the southern flounder and form DNA adducts in target organs.
Department of Medicinal Chemistry, JHMHC, University of Florida, Gainesville 32610.
M O
MO
James
J D
JD
Schell
S M
SM
Boyle
A H
AH
Altman
E A
EA
Cromer
D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000378:metabolism*; D001646:Bile / Q000737:chemistry; D001665:Binding Sites; D001711:Biotransformation; D002274:Carcinogens, Environmental / Q000378:metabolism*; D004247:DNA / Q000008:administration & dosage / Q000378:metabolism*; D018736:DNA Adducts; D004032:Diet; D004101:Dihydroxydihydrobenzopyrenes / Q000008:administration & dosage / Q000378:metabolism*; D005432:Flounder; D014453:Glucuronosyltransferase / Q000378:metabolism; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D008121:Nephropidae
D002274:Carcinogens, Environmental; D018736:DNA Adducts; D004101:Dihydroxydihydrobenzopyrenes; C056612:benzo(a)pyrene-DNA adduct; C017228:benzo(a)pyrene 7,8-dihydrodiol; D001564:Benzo(a)pyrene; D004247:DNA; D014453:Glucuronosyltransferase