Time-varying conjugation of 7,12-dimethylbenz[a]anthracene metabolites in rainbow trout (Oncorhynchus mykiss).
Sexually immature rainbow trout were dosed via gavage with 7,12-[14C]dimethylbenz[a]anthracene (DMBA) in order to study hepatic metabolite formation over time and at single and multiple doses. beta-Glucuronidase and aryl sulfatase hydrolyses of bile extracts and subsequent high-pressure liquid chromatography analysis demonstrated significant levels of sulfate conjugates formed after 12 hr of exposure to a single dose. By 72 hr, glucuronide conjugates had increased and after three doses of [14C]DMBA, glucuronides exceeded the amount of sulfates by almost an order of magnitude. Of the metabolites that could be tentatively identified, the majority were oxidative derivatives of the aromatic rings 3-OH DMBA and 3,4-trans-OHDMBA, the latter of which is mutagenic and a precursor to the proposed ultimate carcinogen of DMBA.
Schnitz
A R
AR
New York University Institute of Environmental Medicine, A. J. Lanza Laboratory, Tuxedo 10987.
Squibb
K S
KS
O'Connor
J M
JM
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001192:Arylsulfatases / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005965:Glucuronates / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D006868:Hydrolysis; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D013431:Sulfates / Q000378:metabolism; D014337:Trout
D005965:Glucuronates; D013431:Sulfates; D015127:9,10-Dimethyl-1,2-benzanthracene; C082250:3-hydroxy-7,12-dimethylbenz(a)anthracene; C024024:7,12-dimethylbenz(a)anthracene-3,4-dihydrodiol; D001192:Arylsulfatases; D005966:Glucuronidase