Biological activity of 2,4,8-trichlorodibenzofuran: promotion of rat liver foci and induction of cytochrome P-450-dependent monooxygenases.
The biological activity of 2,4,8-trichlorodibenzofuran (2,4,8-TCDF) was tested using 2 endpoints: (a) the promotion of enzyme-altered, preneoplastic foci initiated by diethylnitrosamine (DEN) in livers of weanling female Sprague-Dawley rats; and (b) the induction of aryl hydrocarbon (benzo[a]pyrene) hydroxylase (AHH), a marker for cytochrome P-4501 activity, in livers of adult female Sprague-Dawley rats and in H4IIEC3 rat hepatoma cells. When animals were treated with 200 or 500 mg/kg 2,4,8-TCDF 5 X weekly over 10 weeks after a single application of 10 mg/kg DNA, the higher dose of 2,4,8-TCDF had a promoting effect on the appearance of preneoplastic foci. Thus number and total area of foci deficient in adenosine-5'-triphosphatase were significantly increased by a factor of 1.6. 2,4,8-TCDF induced AHH-activities in 9000 X g supernatants of liver 2-3-fold, when rats were treated with 100-1000 mg/kg/day for 5 days and monooxygenase activities determined after another 3 days. The amounts of 2,4,8-TCDF required for inducing AHH activity in H4IIEC3 cells were 7 orders of magnitude higher than those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). the results indicate that the 2,4,8-TCDF has a biological activity which is extremely low compared to that of 2,3,7,8-TCDD.
Deml
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GSF-Institut für Toxikologie, Neuherberg, F.R.G.
Wiebel
F J
FJ
Oesterle
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D
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D001572:Benzofurans / Q000633:toxicity*; D001579:Benzopyrene Hydroxylase / Q000096:biosynthesis*; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010105:Oxygenases / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D001572:Benzofurans; D002273:Carcinogens; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; C063566:2,4,8-trichlorodibenzofuran