Metabolism of 2,2′,3,3′,6,6′-hexachlorobiphenyl and 2,2′,4,4′,5,5′-hexachlorobiphenyl by human hepatic microsomes

Schnellmann, Rick G.; Putnam, Charles W.; Sipes, I. G.

doi:10.1016/0006-2952(83)90209-5

Cited by 69 publications

(96 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PCN and PCB 184 up-regulated CYP3A1 mRNA levels in rat hepatocytes but not CYP3A4 in human cells. The inability of PCBs to induce human CYP3A4 is consistent with previous studies (Farin et al 1994;Schnellmann et al 1983).…”

Section: Resultssupporting

confidence: 91%

“…Ligand-induced activation of SXR is normally achieved at micromolar concentrations, and the mixtures of PCBs existing in certain human tissues could approach these levels (Portigal et al 2002). We note that PCB 153 is one of the most abundant PCBs found in human tissues (Safe 1994) and is not significantly metabolized by human hepatic microsomes (Schnellmann et al 1983). PCB 153 was among the strongest antagonists of human SXR in our experiments (Table 1).…”

Section: Discussionmentioning

confidence: 58%

See 1 more Smart Citation

Highly chlorinated PCBs inhibit the human xenobiotic response mediated by the steroid and xenobiotic receptor (SXR).

Tabb

Kholodovych

Grün

et al. 2004

Environ Health Perspect

116

View full text Add to dashboard Cite

Polychlorinated biphenyls (PCBs) are a family of persistent organic contaminants suspected to cause adverse effects in wildlife and humans. In rodents, PCBs bind to the aryl hydrocarbon (AhR) and pregnane X receptors (PXR) inducing the expression of catabolic cytochrome p450 enzymes of the CYP1A and 3A families. We found that certain highly chlorinated PCBs are potent activators of rodent PXR but antagonize its human ortholog, the steroid and xenobiotic receptor (SXR), inhibiting target gene induction. Thus, exposure to PCBs may blunt the human xenobiotic response, inhibiting the detoxification of steroids, bioactive dietary compounds, and xenobiotics normally mediated by SXR. The antagonistic PCBs are among the most stable and abundant in human tissues. These findings have important implications for understanding the biologic effects of PCB exposure and the use of animal models to predict the attendant risk.

show abstract

Section: Resultssupporting

confidence: 91%

Section: Discussionmentioning

confidence: 58%

Highly chlorinated PCBs inhibit the human xenobiotic response mediated by the steroid and xenobiotic receptor (SXR).

Tabb

Kholodovych

Grün

et al. 2004

Environ Health Perspect

116

View full text Add to dashboard Cite

show abstract

“…Most of the known metabolic pathways involve the initial formation of hydroxylated metabolites. Even one of the more recalcitrant PCBs, CB153, is metabolized in vitro and in vivo to a number of phenolic metabolites (3)(4)(5). Phenolic metabolites can be excreted unchanged, as they were first discovered in the excreta of Baltic seals and Guillemots (6), or further conjugated with glucuronic acid or sulfate (7).…”

mentioning

confidence: 99%

Analysis of hydroxylated metabolites of PCBs (OH-PCBs) and other chlorinated phenolic compounds in whole blood from Canadian inuit.

Sandau

Ayotte

Dewailly

et al. 2000

Environ Health Perspect

179

View full text Add to dashboard Cite

In this study, we identified the main hydroxylated polychlorinated biphenyls (OH-PCBs) and other chlorinated phenolic compounds and we determined their relative concentrations in whole blood from 13 male and 17 female Inuit from northern Quebec, Canada, and from a pooled whole blood sample from southern Quebec. We also determined concentrations of polychlorinated biphenyls (PCBs). Total OH-PCB concentrations were variable among the Inuit samples, ranging over 2 orders of magnitude (0.117-11.6 ng/g whole blood wet weight). These concentradions were equal to and up to 70 times those found for the southern Quebec pooled whole blood sample. Geometric mean concentrations of tota OH-PCBs were 1.73 and 1.01 nglg whole blood for Inuit men and women, respectively, and 0.161 nglg whole blood for the southern population pool. There are limited data available for comparison, but the levels of OH-PCBs in Imuit are higher thn those previously reported in the literature for other populations. There was a significant correlation (p < 0.005) between OH-PCBs and PCBs (r = 0.84) and both correlated significandy (p < 0.005) with age (r= 0.68 and 0.78, respectively). The ratio of OH-PCBs to PCBs was lower in Inuit (0.11) than in the southern Quebec pool (0.33). There is no apparent explanation for the difference. There was considerable variability in the congener pattem of the identified OH-PCBs. The main metabolite, 4-OH-CB109 (4-0H-2,3,3',4',5-pentachlorobiphenyl), constituted 12-62% of the total OH-PCBs in the samples. Pentachlorophenol (PCP) was the dominant phenolic compound in blood, constituting 46% (geometric mean) of the total quantitated chlorinated phenolic compounds. PCP concentrations in Imuit blood ranged from 0.558 to 7.77 ng/g on a wet weight basis. All but two Inuit samples had lower concentrations than the southern Quebec pool (6.29 ng/g). The possible role of OH-PCBs in mediating PCB-induced adverse effects needs to be investigated fiuther.

show abstract

“…TCB metabolism was assessed using the assay of Schnellman et al (Schnellman et al, 1983), as modified by White et al, (1997b).…”

Section: Louis Mo)mentioning

confidence: 99%

Involvement of Cytochrome P450 1A in the toxicity of aryl hydrocarbon receptor agonists : alteration arachidonic acid metabolism and production of reactive oxygen species

Schlezinger¹

1998

View full text Add to dashboard Cite

Metabolism of 2,2′,3,3′,6,6′-hexachlorobiphenyl and 2,2′,4,4′,5,5′-hexachlorobiphenyl by human hepatic microsomes

Cited by 69 publications

References 27 publications

Highly chlorinated PCBs inhibit the human xenobiotic response mediated by the steroid and xenobiotic receptor (SXR).

Highly chlorinated PCBs inhibit the human xenobiotic response mediated by the steroid and xenobiotic receptor (SXR).

Analysis of hydroxylated metabolites of PCBs (OH-PCBs) and other chlorinated phenolic compounds in whole blood from Canadian inuit.

Involvement of Cytochrome P450 1A in the toxicity of aryl hydrocarbon receptor agonists : alteration arachidonic acid metabolism and production of reactive oxygen species

Contact Info

Product

Resources

About