Effect of 2,3,7,8-tetrachlorodibenzoy-p-dioxin on the hepatic 7-ethoxyresorufin O-deethylase activity in four rodent species.
Temporal and dose-related effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hepatic 7-ethoxyresorufin O-deethylase (EROD) activity were investigated in young male Hartley guinea pigs, Sprague-Dawley rats, C57Bl/6 mice, DBA/2 mice and Golden Syrian hamsters. Animals were terminated 1, 7, 14, 28, 56 and 112 days after the administration of a single i.p. dose of TCDD. The maximal induction of EROD activity, at doses producing a similar toxic and limited lethal effect in all species/strains, was 42-, 18-, 7- and 3-fold in rats, DBA/2 mice, C57Bl/6 mice and guinea pigs, respectively. No treatment-related induction of EROD activity was observed in hamsters. Generally, maximal induction occurred 1-4 weeks after injection in all species. The guinea pig alone maintained the same magnitude of induction of EROD activity throughout the study. Observed toxic effects, i.e., lethality, loss of body weight gain, liver enlargement and thymic atrophy, did not correlate with the TCDD-induced hepatic EROD activity. The obtained results suggest that the fold induction of cytochrome P450 1A1 activity is not a critical event for the expression of the lethal effect of TCDD in rodents.
Håkansson
H
H
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Johansson
L
L
Manzoor
E
E
Ahlborg
U G
UG
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006224:Cricetinae; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006168:Guinea Pigs; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013950:Thymus Gland / Q000187:drug effects; D014801:Vitamin A / Q000097:blood
D000072317:Polychlorinated Dibenzodioxins; D014801:Vitamin A; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1