EFFECT OF 2,3,7,8-TETRACHLORODIBENZOY-P-DIOXIN ON THE HEPATIC 7-ETHOXYRESORUFIN-O-DEETHYLASE ACTIVITY IN 4 RODENT SPECIES

Temporal and dose-related effects of 2,3,7,8-tetrachlorodibenzo-p-diox in (TCDD) on hepatic 7-ethoxyresorufin 0-deethylase (EROD) activity we re investigated in young male Hartley guinea pigs, Sprague-Dawley rats , C57B1/6 mice, DBA/2 mice and Golden Syrian hamsters. Animals were te rminated 1, 7, 14, 28, 56 and 112 days after the administration of a s ingle i.p. dose of TCDD. The maximal induction of EROD activity, at do ses producing a similar toxic and limited lethal effect in all species /strains, was 42-, 18-, 7- and 3-fold in rats, DBA/2 mice, C57B1/6 mic e and guinea pigs, respectively. No treatment-related induction of ERO D activity was observed in hamsters. Generally, maximal induction occu rred 1-4 weeks after injection in all species. The guinea pig alone ma intained the same magnitude of induction of EROD activity throughout t he study. Observed toxic effects, i.e., lethality, loss of body weight gain, liver enlargement and thymic atrophy, did not correlate with th e TCDD-induced hepatic EROD activity. The obtained results suggest tha t the fold induction of cytochrome P450 1A1 activity is not a critical event for the expression of the lethal effect of TCDD in rodents.