Specific human CYP 450 isoform metabolism of a pentachlorobiphenyl (PCB-IUPAC# 101)

McGraw, Joseph; Waller, Donald P.

doi:10.1016/j.bbrc.2006.03.122

Cited by 41 publications

(51 citation statements)

References 21 publications

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“…Structurally different PCB congeners may be metabolized by different enzymes of the CYP superfamily. Non-ortho substituted (so called co-planar or dioxin-like) PCB congeners are metabolized predominately by CYP1A enzymes, while multiple ortho-substituted PCBs are substrates for CYP2B enzymes (Kaminsky et al, 1981, Lu et al, 2013, Lu and Wong, 2011, McGraw and Waller, 2006, Waller et al, 1999, Warner et al, 2009). These observations are also confirmed by more efficient binding of structurally related PCBs to appropriate cytochrome P-450 isoforms (Hrycay and Bandiera, 2003, Kania-Korwel et al, 2008a).…”

Section: Pcb Metabolism and Relevant Classes Of Pcb Metabolitesmentioning

confidence: 99%

Metabolism and metabolites of polychlorinated biphenyls

Grimm

Kania-Korwel

et al. 2015

Critical Reviews in Toxicology

369

414

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The metabolism of polychlorinated biphenyls (PCBs) is complex and has an impact on toxicity and thereby assessment of PCB risks. A large number of reactive and stable metabolites are formed in the processes of biotransformation in biota in general and in humans in particular. The aim of this document is to provide an overview of PCB metabolism and to identify metabolites of concern and their occurrence. Emphasis is given to mammalian metabolism of PCBs and their hydroxyl, methylsulfonyl, and sulfated metabolites, especially those that persist in human blood. Potential intracellular targets and health risks are also discussed.

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Section: Pcb Metabolism and Relevant Classes Of Pcb Metabolitesmentioning

confidence: 99%

Metabolism and metabolites of polychlorinated biphenyls

Grimm

Kania-Korwel

et al. 2015

Critical Reviews in Toxicology

369

414

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“…12,13 These earlier studies identified P450 2A6 as the primary P450 isoform involved in the para-oxidation of a 2,5-dichloro substituted phenyl ring. In contrast, PCB 136 (2,2′,3,3′,6,6′-hexachlorobiphenyl), a symmetrical congener with two 2,3,6-trichloro substituted phenyl rings, is oxidized by pHLMs to both para- and meta-hydroxylated metabolites.…”

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confidence: 97%

2,2′,3,5′,6-Pentachlorobiphenyl (PCB 95) Is Atropselectively Metabolized to para-Hydroxylated Metabolites by Human Liver Microsomes

Uwimana

Lehmler

2016

Chem. Res. Toxicol.

117

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Exposure to neurotoxic, chiral PCBs has been associated with neurodevelopmental disorders, but their metabolism in humans remains unexplored. We investigated the enantioselective metabolism of PCB 95 by human liver microsomes (HLMs) to potentially neurotoxic, hydroxylated metabolites (OH-PCBs). OH-PCB profiles formed in experiments with HLMs differed from metabolite profiles reported for rodent species. The second eluting atropisomer of 2,2′,3,5′,6-pentachlorobiphenyl-4′-ol, the major metabolite, was preferentially formed by all HLM preparations investigated. Differences in metabolite formation rates were observed with single donor HLMs. The metabolism of PCBs and its role in PCB-mediated neurodevelopmental disorders need to be further characterized.

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“…GC methods used were as described in McGraw and Waller [13]. However, only PCB 101 provided a detectable product through screening runs with GC/ECD.…”

Section: Methodsmentioning

confidence: 99%

“…The Chicago Great Lakes cohort of pregnant African American women was developed to study organochlorine exposure through Great Lakes resources in a pregnant African American population and their children [12,13]. Within the GLCPAAW, PCB 101 and 118 were found in higher concentrations in those who reported exclusive African American descent versus mixed race/ethnicity.…”

Section: Introductionmentioning

confidence: 99%

The role of African American ethnicity and metabolism in sentinel polychlorinated biphenyl congener serum levels

McGraw

Waller

2009

Environmental Toxicology and Pharmacology

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Polychlorinated biphenyls (PCBs) are environmental contaminants found in the serum of human populations across the globe. A small set of sentinel PCB congeners (IUPAC# 101, 118, 138, 153, and 180) commonly sought in human serum are often used as markers of exposure. The Chicago Great Lakes cohort of pregnant African American women was developed to study organochlorine exposure through Great Lakes resources in a pregnant African American population and their children. Comparison of PCB serum concentrations in women reporting mixed race/ethnicity within the cohort shows significant elevations of serum PCB 101 and 118 in women reporting exclusive African American ancestry.Incubations were performed using pooled human liver microsomes followed by individual recombinant human CYP isoform microsomes to identify whether the other sentinel congeners are metabolized by human CYP 450. In human liver microsome metabolism experiments with the sentinel PCB congeners (IUPAC# 101, 118, 138, 153, and 180), only PCB 101 metabolism produced an identifiable metabolite. However, a significant loss of parent compound was observed for PCB 118 incubations with human liver microsomes. The loss of PCB 101 and PCB 118 in microsome experiments indicates they are likely metabolized in human liver. Therefore, CYP 450 mediated metabolic differences may contribute to differences in serum concentrations by race/ethnicity. PCB metabolism has an important impact on toxicity. PCB metabolites have been shown to differ significantly in toxicity profiles relative to parent compounds. Biomonitoring studies of PCB serum levels have correlated with toxicity for the metabolizeable congeners such as PCB 101 and PCB 118. However, measureable amounts of metabolizeable parent congeners such as PCB 101 may not be detectable in the serum of study participants. Because PCB 118 is metabolized, but is also readily found in human serum, it may be a better marker of metabolism related PCB toxicity. Human specific PCB metabolism is difficult to characterize but has important pathophysiological ramifications and deserves further study.

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Specific human CYP 450 isoform metabolism of a pentachlorobiphenyl (PCB-IUPAC# 101)

Cited by 41 publications

References 21 publications

Metabolism and metabolites of polychlorinated biphenyls

Metabolism and metabolites of polychlorinated biphenyls

2,2′,3,5′,6-Pentachlorobiphenyl (PCB 95) Is Atropselectively Metabolized to para-Hydroxylated Metabolites by Human Liver Microsomes

The role of African American ethnicity and metabolism in sentinel polychlorinated biphenyl congener serum levels

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