Biological activity of 2,4,8-trichlorodibenzofuran: promotion of rat liver foci and induction of cytochrome P-450-dependent monooxygenases

Abstract

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][prynene) hydroxylase (AHH), a marker for cytochrome P-450I 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 × weekly over 10 weeks after a single application of 10 mg/kg DEN, 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′-triphosphate were significantly increased by a factor of 1.6. 2,4,8-TCDF induced AHH-activities in 9000 × g supernatants of liver 2—-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.