Uptake, toxicity, and distribution of benzo[a]pyrene and monooxygenase induction in the topminnows Poeciliopsis monacha and Poeciliopsis lucida.
Poeciliopsis lucida and Poeciliopsis monacha are freshwater viviparous fishes susceptible to tumorigenesis by brief exposure to waterborne procarcinogens. The hepatic monooxygenase system and the uptake, toxicity, and distribution of benzo[a]pyrene (BP) were characterized as a first step in exploring relationships between xenobiotic metabolism and cancer in these fishes. Waterborne BP was lethal at a dose of 3.75 mg/liter with a 24-hr exposure. During a 24-hr exposure to 1.0 mg/liter (3.97 mumol/liter) [3H]BP, an average of 8.27 nmol of BP was taken up per fish. Of this total, 64-70% was in the gallbladder or gut, indicating rapid metabolism and excretion. Basal levels of aryl hydrocarbon hydroxylase (AHH) activity were fairly high, about 0.6 nmol/min/mg. Maximal induction by BP occurred at a dose of 1.0 mg/liter, but with AHH activities only about twice the levels in untreated fish. Sensitivity to inhibition by alpha-naphthoflavone (ANF) increased slightly in treated fish. Induced AHH and also 7-ethoxyresorufin O-deethylase (EROD) activities declined slowly after a single treatment, approaching pre-exposure levels after 7 days. Monoclonal and polyclonal antibodies to cytochrome P-450E, the AHH and EROD catalyst in the marine fish scup (Stenotomus chrysops), inhibited AHH and EROD activities in untreated Poeciliopsis, indicating structural similarity between the catalysts in these fish species. Untreated Poeciliopsis evidently contain a counterpart to scup cytochrome P-450E, the major polycyclic aromatic hydrocarbon-inducible from in scup. High levels of basal activity and the pattern of monooxygenase induction could be involved in the sensitivity of these fishes to polycyclic aromatic hydrocarbon and other procarcinogens.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D001564:Benzo(a)pyrene / Q000493:pharmacokinetics* / Q000633:toxicity; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004790:Enzyme Induction / Q000187:drug effects; D005399:Fishes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology; D010088:Oxidoreductases / Q000096:biosynthesis*; D014018:Tissue Distribution
D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1