Rainbow trout hepatic mixed-function oxygenase induction by polychlorinated dibenzo-p-dioxins (PCDDs) as a function of time and tissue concentration.
Rainbow trout, dosed orally with 0.060-84 micrograms/kg of [3H]-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), [14C]-1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (HxCDD), or [14C]-1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) showed dose-dependent increases in hepatic ethoxyresorufin O-deethylase (EROD) activity, up to 250-fold, after 2-16 d. Induction of EROD activity was a sensitive and rapid indicator of exposure to PCDDs. The effects of time after exposure were not dramatic, but generally EROD activity after 2 d was lower than EROD activity after 16 d. Slopes of dose-response curves relating EROD activity to hepatic concentrations of PCDDs significantly decreased and intercepts significantly increased with increasing time of exposure. When fish were grouped by oral doses, only the low doses of TCDD and HpCDD exhibited time-dependent EROD induction, with significantly greater activity 16 d after dosing compared to 2 d. In most cases, hepatic and muscle concentrations of PCDDs did not significantly change over time. Concentrations of PCDDs in liver and muscle accounted for up to 7% of the orally administered dose. Hepatic levels of PCDDs ranged from 20-100 pg/g at the lowest doses to about 1000 pg TCDD/g, 2000 pg HxCDD/g, or 40,000 pg HpCDD/g at the highest doses. Of the PCDD in the liver, approximately one-third to one-half was associated with the postmitochondrial supernatant (PMS). PCDD concentrations in muscle did not span as wide a range of concentrations as did PCDD in liver; fish given low doses had 10 pg/g in muscle whereas fish given high doses had several hundred picograms per gram in muscle for all three PCDDs.
D000818:Animals; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D017686:Oncorhynchus mykiss; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution
D000072317:Polychlorinated Dibenzodioxins; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1