The biologic and toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in chickens.
The administration of 2,3,7,8-TCDD to 2-week-old White Leghorn cockerels produced a dose-dependent induction of hepatic microsomal ethoxyresorufin O-deethylase (EROD) and benzo[alpha]pyrene (B[alpha]P) hydroxylase activities with induction EC50 values of 778 and 302 ng/kg, respectively. In addition, 2,3,7,8-TCDD also induced 4-dimethylaminoantipyrine (DMAP) N-demethylase (EC50 = 561 ng/kg), this result contrasting with studies reported for other animal species in which 2,3,7,8-TCDD either does not induce or inhibits this cytochrome P-450 dependent monooxygenase enzyme activity. However, the reduced cytochrome P-450:CO binding difference spectral absorption maxima for the 2,3,7,8-TCDD induced microsomes was observed at 448 nm which was similar to that reported for most animals which have been investigated. Electrophoresis of control and 2,3,7,8-TCDD induced microsomal proteins using SDS polyacrylamide slab gels showed intensification of 3 protein staining bands at Mr 53 000, 56 000 and 58 000. Incubation of the 2,3,7,8-TCDD-induced microsomes with SKF-525A and alpha-naphthoflavone showed that both compounds inhibited DMAP N-demethylase, EROD and AHH and that alpha-naphthoflavone was the more potent inhibitor of all 3 microsomal monooxygenases. 2,3,7,8-TCDD treatment caused significant involution of the Bursa of Fabricius when administered at a dose level of 10 micrograms/kg for 3 days and this result confirmed the extreme sensitivity of the immature White Leghorn cockerel to the biologic and toxic effects elicited by 2,3,7,8-TCDD. However, in contrast to other sensitive species, no high affinity cytosolic receptor protein for [3H]2,3,7,8-TCDD could be detected in the liver of chick embryos or 2-week-old birds.
Sawyer
T
T
Jones
D
D
Rosanoff
K
K
Mason
G
G
Piskorska-Pliszczynska
J
J
Safe
S
S
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D001579:Benzopyrene Hydroxylase / Q000096:biosynthesis; D002499:Centrifugation, Density Gradient; D002645:Chickens; D019363:Cytochrome P-450 CYP1A1; D003600:Cytosol / Q000378:metabolism; D004147:Dioxins / Q000633:toxicity*; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D010088:Oxidoreductases / Q000096:biosynthesis; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; C019647:aldrin epoxidase; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D010089:Oxidoreductases, N-Demethylating; C023680:dimethylaminoantipyrine N-demethylase