title: Biotransformation, hepatopancreas DNA binding and pharmacokinetics of benzo[a]pyrene after oral and parenteral administration to the American lobster, Homarus americanus.
abstract: It has been shown that American lobsters, (Homarus americanus) environmentally exposed to polycyclic aromatic hydrocarbons do not develop tumors or neoplastic changes although finfish exposed under identical conditions do develop cancer. In this study, environmentally relevant doses (nominally 50 micrograms/kg) of a radiolabelled model procarcinogen, benzo[a]pyrene (BaP), were administered i.v. or p.o. to lobsters and the fate of the radiolabel examined. Parent BaP was rapidly distributed from hemolymph into tissues after i.v. administration. Following oral administration, hemolymph concentrations of BaP rose slowly and reached levels similar to those found after i.v. administration by 48 h after the dose. The tissue distribution of BaP residues was determined at 3 days, 2 weeks and 4 weeks after the p.o. dose and 2 weeks after the i.v. dose. There was no route-related difference in tissue concentrations of BaP residues at 2 weeks. At all times, most of the retained BaP residues were in hepatopancreas (25-75% administered dose) or muscle (8-42% administered dose). Greater than 93% of the radioactivity in muscle was parent BaP at all studied times and the mean concentration of BaP residues in muscle was constant over the period of study. Although most of the radioactivity in hepatopancreas was BaP, metabolites were found and BaP residues declined with time. DNA isolated from hepatopancreas showed extremely low levels of BaP-metabolite binding, 0.016 +/- 0.013 pmol BaP equivalents/mg DNA, mean +/- S.D., n = 11. These studies show that BaP from dietary sources is retained for long periods by edible lobster tissues and suggest that a major reason for the resistance of American lobsters to polycyclic aromatic hydrocarbon-induced cancers is the very slow phase 1 metabolism to reactive metabolites.
authors.affiliation: Department of Medicinal Chemistry, University of Florida, Gainesville 32610-0485.
authors.forename: M O
authors.initials: MO
authors.lastname: James
authors.forename: A H
authors.initials: AH
authors.lastname: Altman
authors.forename: C L
authors.initials: CL
authors.lastname: Li
authors.forename: J D
authors.initials: JD
authors.lastname: Schell
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism* / Q000493:pharmacokinetics*; D001711:Biotransformation; D002250:Carbon Radioisotopes; D004247:DNA / Q000378:metabolism*; D005260:Female; D006458:Hemolymph / Q000378:metabolism; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000378:metabolism; D008121:Nephropidae / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism*; D014018:Tissue Distribution; D014316:Tritium
chemical_list: D002250:Carbon Radioisotopes; D014316:Tritium; D001564:Benzo(a)pyrene; D004247:DNA