Biomaterial Database

Interactive effects between 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,2',4,4',5,5'-hexachlorobiphenyl in female B6C3F1 mice: tissue distribution and tissue-specific enzyme induction. 1996

A P van Birgelen, and D G Ross, and M J DeVito, and L S Birnbaum

National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.

The distribution of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) was studied in female B6C3F1 mice. Single doses of TCDD alone (0, 0.1, 1, or 10 micrograms [3H]TCDD/kg), PCB 153 alone (0, 3.58, 35.8, or 358 mg [14C]PCB 153/kg), and all possible combinations of these doses were administered in corn oil, po. At 7 days after dosing, 11 different tissues were analyzed for radioactivity. When TCDD was administered alone, TCDD-derived radioactivity distributed to all tissues in a dose-dependent manner, increasing with dose in the liver, while decreasing (as a percentage of the administered dose) in all other tissues. When PCB 153 was administered alone, the PCB 153 concentration was dose-dependently (percentage of dose) decreased in liver, skin, lung, adrenals, kidney, and blood; no dosimetric effects were observed in the other organs. Coadministration of low doses of both TCDD and PCB 153 resulted in little or no effect on the distribution of either compound. Interactive effects occurred in the pharmacokinetic behavior of both compounds only at higher doses. For example, the amount of TCDD in the liver was increased by 358 mg PCB 153/kg. In most other organs administration of PCB 153 resulted in a dose-dependent decrease in the TCDD content. Coadministration of PCB 153 with 10 micrograms TCDD/kg increased PCB 153 in the liver, but not in other tissues. These results clearly demonstrate that interactive effects on pharmacokinetic behavior occur only at high doses.

UI	MeSH Term	Description	Entries
D007527	Isoenzymes	Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.	Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008168	Lung	Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.	Lungs
D008297	Male		Males
D009929	Organ Size	The measurement of an organ in volume, mass, or heaviness.	Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D011078	Polychlorinated Biphenyls	Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants.	PCBs,Polychlorinated Biphenyl,Polychlorobiphenyl Compounds,Biphenyl, Polychlorinated,Biphenyls, Polychlorinated,Compounds, Polychlorobiphenyl
D001835	Body Weight	The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.	Body Weights,Weight, Body,Weights, Body
D003577	Cytochrome P-450 Enzyme System	A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.	Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
D004790	Enzyme Induction	An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.	Induction, Enzyme