hexachlorodibenzo-4-dioxin and Body-Weight

The structure-activity relationships between the mixed-function oxidase (MFO) system and six polychlorinated derivatives of dibenzo-p-dioxin (PCDDs) were studied using Sprague Dawley rats. The study was set up in accordance with previous work in these laboratories involving monocyclic hydrocarbons. Three possible mechanisms at the MFO active site are proposed. C-H bond hydroxylation in low chlorine substituted PCDDs, and probable expoxidation in the intermediate chlorinated species including 2378 tetrachlorodibenzodioxin. Benzo[a]pyrene activity induced by some PCDDs appears irrelevant to the desired metabolic result.

Topics: Animals; Benzo(a)pyrene; Body Weight; Chemical Phenomena; Chemistry, Physical; Dioxins; Enzyme Induction; Liver; Mixed Function Oxygenases; NADP; Polychlorinated Dibenzodioxins; Rats; Rats, Inbred Strains; Structure-Activity Relationship; Substrate Specificity

A single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7-tribromodibenzo-p-dioxin (2,3,7-TBDD), 1,2,3,7,8,9-hexachlorodibenzo-p-dioxin (1,2,3,7,8,9-HCDD), 1,2,4,6,7,9-hexachlorodibenzo-p-dioxin (1,2,4,6,7,9-HCDD), or 1,3,6,8-tetrachlorodibenzo-p-dioxin (1,3,6,8-TCDD) was given to male rats (25 micrograms/kg, p.o.) and plasma concentration and biliary excretion of ouabain assessed 10 days later. Treatment of TCDD, 2,3,7-TBDD and to a lesser extent 1,2,3,7,8,9-HCDD increased the plasma concentration of ouabain and decreased its excretion into ouabain. TCDD, 2,3,7-TBDD and to a lesser extent, 1,2,3,7,8,9-HCDD decreased the bile flow. Liver wet weight was increased in TCDD and 2,3,7-TBDD treated rats. The magnitude of depression in ouabain excretion by those compounds was closely related to the reported relative binding affinity of the compound to liver cytosol and their induction potency of aryl hydrocarbon hydroxylase activity.

Topics: Animals; Bile; Body Weight; Dioxins; Liver; Male; Ouabain; Polychlorinated Dibenzodioxins; Rats; Rats, Inbred Strains