Induction of Cytochrome P450 Isoenzymes after Toxicokinetic Interactions between 2,3,7,8-Tetrachlorodibenzo-p-dioxin and 2,2′,4,4′,5,5′-Hexachlorobiphenyl in the Liver of the Mouse

Jongh, Joost de; DeVito, Michael J.; Nieboer, Ruud; Birnbaum, Linda S.; Berg, Martin van den

doi:10.1006/faat.1995.1062

Cited by 24 publications

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“…However, antagonistic as well as synergistic effects have been found after co-administration of binary mixtures in single-dose, short-term experiments in rodents using hepatic cytochrome P450 isozymes, immunotoxicity, and teratogenicity as endpoints (29)(30)(31)(32)(33). After chronic exposure to 2,2',4,4',5,5'-and 3,3',4, 4',5,5'-hexabromobiphenyl in rats, Jensen and Sleight (34) found synergism in hepatic tumor promotion.…”

mentioning

confidence: 99%

Synergistic effect of 2,2',4,4',5,5'-hexachlorobiphenyl and 2,3,7,8-tetrachlorodibenzo-p-dioxin on hepatic porphyrin levels in the rat.

Birgelen

Fase

Kolk

et al. 1996

Environ Health Perspect

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We studied the effect of polychlorinated biphenyls (PCBs) on hepatic porphyrin accumulation in female Sprague-Dawley rats by feeding them diets containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), 2,3,3',4,4',5-hexachlorobiphenyl (PCB 156), 3,3',4,4',5-pentachlorobiphenyl (PCB 126), or combinations of the single PCB congeners with TCDD for 13 weeks. A dose-dependent increase in hepatic porphyrin accumulation occurred after TCDD, PCB 126, or PCB 156 administration, reaching maximal levels of about twice control values. The lowest dose levels for which a significant increase in hepatic porphyrin accumulation was found were 0.7 microgram TCDD/kg diet, 50 micrograms PCB 126/kg diet, or 6 mg PCB 156/kg diet. These doses are equivalent to 47 ng TCDD/kg/day, 3.2 micrograms PCB 126/kg/day, and 365 micrograms PCB 156/kg/day. Relative potencies for hepatic porphyrin accumulation, using TCDD as a reference, ranged from 0.015 to 0.06 for PCB 126 and from 0.0001 to 0.0003 for PCB 156. CYP1A2 activities significantly correlated with hepatic porphyrin levels, with coefficients of 0.629, 0.483, or 0.808 for TCDD, PCB 126, or PCB 156, respectively. Administration of PCB 153 alone did not result in hepatic porphyrin accumulation. Co-administration of PCB 153 and TCDD revealed a strong synergistic effect on porphyrin accumulation (about 800 times control levels). This synergistic effect was significant in rats fed diets containing any combination of PCB 153 with TCDD. Uroporphyrin III and heptacarboxylic porphyrin were accumulated in porphyrinogenic livers. These results suggest that TCDD induction of CYP1A2 may be involved, leading to oxidation of uroporphyrinogen III to uroporphyrin III, in combination with an increase in delta-aminolevulinic acid synthetase induced by PCB 153. Under porphyrinogenic conditions, an inhibitor of CYP1A2 activity may also be formed. The interactive effects on porphyrin accumulation after co-administration of dioxinlike and non-dioxinlike compounds may have significant implications for the risk assessment of these chemicals.ImagesFigure 1.Figure 1.Figure 1.Figure 2.

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mentioning

confidence: 99%

Synergistic effect of 2,2',4,4',5,5'-hexachlorobiphenyl and 2,3,7,8-tetrachlorodibenzo-p-dioxin on hepatic porphyrin levels in the rat.

Birgelen

Fase

Kolk

et al. 1996

Environ Health Perspect

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“…The increasing ratio of CBs 126/110 in liver residues is partly due to the labile 2,3,6-substituted ring (Bruhn et al 1995;Hansen 1979Hansen , 1987 coupled with dramatic enzyme induction at even the lowest dose of CB 110C; however, this is further magnified by the propensity of coplanar chlorinated aromatics to accumulate in livers. The high liver deposition of TCDD and dioxin-like compounds has been reported in several studies (Curtis et al 1990;Kedderis et al 1991;De Jongh et al 1995).…”

Section: Residue Depositionmentioning

confidence: 74%

“…In the previous study, a similar maximum induction of EROD activity was observed for the environmental mixture within the same dose range while PROD activity was suppressed by Ah-receptor agonists, as evidenced by similar dose-dependent induction when these compounds were removed by activated charcoal (Li and Hansen 1996a). Ah-receptor agonists have also been shown to antagonize induction of PROD activity and/or other measures of CYP2B in mouse liver (De Jongh et al 1995).…”

Section: Enzyme Inductionmentioning

confidence: 99%

Hepatic Enzyme Induction and Acute Endocrine Effects of 2,3,3',4',6-Pentachlorobiphenyl in Prepubertal Female Rats

Rhine

Hansen

1998

Archives of Environmental Contamination and Toxicology

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Polychlorinated biphenyls (PCBs) with the labile 2,3,6-substitution are important components of atmospheric and certain food chain exposures, but little is known about their biological activities. Chlorobiphenyl 110 (2,3,3',4',6-pentaCB) was investigated in weanling female rats dosed ip on days 21 and 22 and killed on day 23 of age. The initial preparation of CB 110 markedly induced 7-ethoxyresorufin O-dealkylase (EROD) activity and was found to be contaminated with coplanar 3,3',4,4',5-pentaCB (CB 126). The contaminated preparation (CB 110C) was purified with activated charcoal (CB 110P). The CB 110P induced pentoxyresorufin O-dealkylase (PROD), was weakly uterotropic and a modest depleter of serum thyroxine (T4). CB 110C caused increased liver weight, induced EROD, PROD, and UDP glucuronyl transferase activities and caused a greater depletion of serum T4; on the other hand, it suppressed the PROD induction and the uterotropic effect of CB 110P. Hepatic residues of CB 110 were a constant 2-3% of the dose while those of CB 126 (from CB 110C) increased with increasing dose to as much as 50% of the dose.

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Dibenzo‐p‐Dioxins: 2,3,7,8‐Tetrachlorodibenzo‐p‐Dioxin

Reid¹

2002

Encyclopedia of Agrochemicals

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Dibenzo‐ p ‐dioxins are a class of compounds of which there are 75 possible isomers as shown. A recent IARC Monograph summarizes much of the information on these compounds. By far, the majority of the information is for 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin (TCDD), the most toxic of the isomers. Most of the material in this chapter relates to this compound.

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Induction of Cytochrome P450 Isoenzymes after Toxicokinetic Interactions between 2,3,7,8-Tetrachlorodibenzo-p-dioxin and 2,2′,4,4′,5,5′-Hexachlorobiphenyl in the Liver of the Mouse

Cited by 24 publications

References 0 publications

Synergistic effect of 2,2',4,4',5,5'-hexachlorobiphenyl and 2,3,7,8-tetrachlorodibenzo-p-dioxin on hepatic porphyrin levels in the rat.

Synergistic effect of 2,2',4,4',5,5'-hexachlorobiphenyl and 2,3,7,8-tetrachlorodibenzo-p-dioxin on hepatic porphyrin levels in the rat.

Hepatic Enzyme Induction and Acute Endocrine Effects of 2,3,3',4',6-Pentachlorobiphenyl in Prepubertal Female Rats

Dibenzo‐p‐Dioxins: 2,3,7,8‐Tetrachlorodibenzo‐p‐Dioxin

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