Aryl hydrocarbon hydroxylase activity in F-344 rats subchronically exposed to benzo(a)pyrene and fluoranthene through diet.
In order to investigate the relationship between aryl hydrocarbon hydroxylase (AHH) activity and exposure to benzo[a]pyrene [B(a)p] and fluoranthene (FLA), AHH activities in liver tissues of male and female F-344 rats were determined. Based on a range-finding study, doses of 0, 5, 50, and 100 mg/kg B(a)p or 0, 150, 750, and 1500 mg/kg FLA were administered in the animal diet over a 90-day period. After dosing, animals were sacrificed, liver tissues were removed, and microsomes were isolated. AHH activities were determined by reverse-phase HPLC coupled with fluorescence detection using 3-hydroxy B(a)p, and trans-2,3-dihydroxy-1,10-epoxy-1,2,3,10b tetrahydrofluoranthene as the standards. A dose-dependent increase in enzyme activity was observed with increased B(a)p or FLA exposure in both males and females. Our results also demonstrate that B(a)p-exposed females possess a higher AHH activity than males, but there is no significant sex difference with regard to enzyme activity in the case of FLA at higher doses. Overall, our findings suggest that long-term exposure to the parent compound results in elevated levels of AHH activity, which may contribute to the formation of toxic reactive metabolites and subsequent symptoms in target organs.
Ramesh
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Department of Pharmacology, Meharry Medical College, Nashville, TN 37208, USA. aramesh@ccvax.mmc.edu
Inyang
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F
Hood
D B
DB
Knuckles
M E
ME
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D001564:Benzo(a)pyrene / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D005449:Fluorenes; D001564:Benzo(a)pyrene; C007738:fluoranthene; D001189:Aryl Hydrocarbon Hydroxylases