Evidence map›Paper›PMID 30576102›Full record

ArticleEnvironmental science & technology2019

Human CYP2A6, CYP2B6, AND CYP2E1 Atropselectively Metabolize Polychlorinated Biphenyls to Hydroxylated Metabolites.

Eric Uwimana, Patricia Ruiz, Xueshu Li, Hans-Joachim Lehmler

Abstract read
In one paragraph

Article in Environmental science & technology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
4.7field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 49 citations in OpenAlex.

  1. Expression of the Human R163C-International journal of molecular sciences · 2026
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  12. Gene×environment interactions in autism spectrum disorders.Current topics in developmental biology · 2023
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Eric UwimanaInterdisciplinary Graduate Program in Human Toxicology and Department of Occupational and Environmental Health , University of Iowa , Iowa City , Iowa 52242 , United States.ORCID 0000-0003-0653-1155
Patricia RuizDivision of Toxicology and Human Health Sciences, Computational Toxicology and Methods Development Lab , Agency for Toxic Substances and Disease Registry , Atlanta , Georgia 30333 , United States.
Xueshu LiInterdisciplinary Graduate Program in Human Toxicology and Department of Occupational and Environmental Health , University of Iowa , Iowa City , Iowa 52242 , United States.
Hans-Joachim LehmlerInterdisciplinary Graduate Program in Human Toxicology and Department of Occupational and Environmental Health , University of Iowa , Iowa City , Iowa 52242 , United States.ORCID 0000-0001-9163-927X
University of Iowa · USAgency for Toxic Substances and Disease Registry · US

Funding

Training CoreP42ES013661 · NIEHS · UNIVERSITY OF IOWA · PI Rachel Frances Marek · 2006 to 2026
$60.3M
Pulmonary Toxicology Facility CoreP30ES005605 · NIEHS · UNIVERSITY OF IOWA · PI Jong Sung Kim · 1990 to 2026
$40.5M
PCB Enantiomers Implicated in Neurodevelopmental Disorders: Identification of Individual Metabolic Factors that Determine Risk and VulnerabilityR21ES027169 · NIEHS · UNIVERSITY OF IOWA · PI LEHMLER, HANS-JOACHIM · 2017 to 2018
$410k
NIEHS NIH HHS P30 ES005605NIEHS NIH HHS P42 ES013661NIEHS NIH HHS R21 ES027169
6 · The paper itself

Abstract

Exposure to chiral polychlorinated biphenyls (PCBs) has been associated with neurodevelopmental disorders. Their hydroxylated metabolites (OH-PCBs) are also potentially toxic to the developing human brain; however, the formation of OH-PCBs by human cytochrome P450 (P450) isoforms is poorly investigated. To address this knowledge gap, we investigated the atropselective biotransformation of 2,2',3,4',6-pentachlorobiphenyl (PCB 91), 2,2',3,5',6-pentachlorobiphenyl (PCB 95), 2,2',3,3',4,6'-hexachlorobiphenyl (PCB 132), and 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) by different human P450 isoforms. In silico predictions with ADMET Predictor and MetaDrug software suggested a role of CYP1A2, CYP2A6, CYP2B6, CYP2E1, and CYP3A4 in the metabolism of chiral PCBs. Metabolism studies with recombinant human enzymes demonstrated that CYP2A6 and CYP2B6 oxidized PCB 91 and PCB 132 in the meta position and that CYP2A6 oxidized PCB 95 and PCB 136 in the para position. CYP2B6 played only a minor role in the metabolism of PCB 95 and PCB 136 and formed meta-hydroxylated metabolites. Traces of para-hydroxylated PCB metabolites were detected in incubations with CYP2E1. No hydroxylated metabolites were present in incubations with CYP1A2 or CYP3A4. Atropselective analysis revealed P450 isoform-dependent and congener-specific atropselective enrichment of OH-PCB metabolites. These findings suggest that CYP2A6 and CYP2B6 play an important role in the oxidation of neurotoxic PCBs to chiral OH-PCBs in humans.

Indexed as

Polychlorinated BiphenylsCytochrome P-450 CYP2A6Cytochrome P-450 CYP2B6Cytochrome P-450 CYP2E1HumansHydroxylationStereoisomerismCYP2A6 protein, humanCYP2B6 protein, humanCytochrome P-450 CYP2A6Cytochrome P-450 CYP2B6Cytochrome P-450 CYP2E1Polychlorinated Biphenyls

Identifiers

PMID30576102
PMCPMC6380921
OpenAlexW2906450567

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.