Journal article
Human Liver Microsomes Atropselectively Metabolize 2,2',3,4',6-Pentachlorobiphenyl (PCB 91) to a 1,2-Shift Product as the Major Metabolite
Environmental science & technology, Vol.52(10), pp.6000-6008
05/15/2018
DOI: 10.1021/acs.est.8b00612
PMCID: PMC5966832
PMID: 29659268
Abstract
Polychlorinated biphenlys (PCBs) and their hydroxylated metabolites (OH-PCBs) have been implicated in neurodevelopmental disorders. Several neurotoxic PCBs, such as PCB 91, are chiral because they form stable rotational isomers, or atropisomers, that are nonsuperimposable mirror images of each other. Because only limited information about the metabolism of these PCBs by human cytochrome P450 (P450) enzymes is available, we investigated the biotransformation of PCB 91 to OH-PCBs by human liver microsomes (HLMs). Racemic PCB 91 was incubated with pooled or individual donor HLMs at 37 °C, and levels and chiral signatures of PCB 91 and its metabolites were determined. Several OH-PCBs were formed in the order 2,2',4,4',6-pentachlorobiphenyl-3-ol (3-100; 1,2 shift product) > 2,2',3,4',6-pentachlorobiphenyl-5-ol (5-91) ≫ 2,2',3,4',6-pentachlorobiphenyl-4-ol (4-91) ≫ 4,5-dihydroxy-2,2',3,4',6-pentachlorobiphenyl (4,5-91). Metabolite formation rates displayed interindividual variability. The first eluting atropisomers of PCB 91, 3-100 and 4-91, and the second eluting atropisomer of 5-91 were enriched in most metabolism studies. The unexpected, preferential formation of a 1,2-shift product and the variability of the OH-PCBs profiles in experiments with individual donor HLMs underline the need for further systematic studies of the atropselective metabolism of PCBs in humans.
Details
- Title: Subtitle
- Human Liver Microsomes Atropselectively Metabolize 2,2',3,4',6-Pentachlorobiphenyl (PCB 91) to a 1,2-Shift Product as the Major Metabolite
- Creators
- Eric Uwimana - Department of Occupational and Environmental Health , The University of Iowa , #164 MTF, Iowa City , Iowa 52242-5000 , United StatesXueshu Li - Department of Occupational and Environmental Health , The University of Iowa , #164 MTF, Iowa City , Iowa 52242-5000 , United StatesHans-Joachim Lehmler - Department of Occupational and Environmental Health , The University of Iowa , #164 MTF, Iowa City , Iowa 52242-5000 , United States
- Resource Type
- Journal article
- Publication Details
- Environmental science & technology, Vol.52(10), pp.6000-6008
- DOI
- 10.1021/acs.est.8b00612
- PMID
- 29659268
- PMCID
- PMC5966832
- NLM abbreviation
- Environ Sci Technol
- ISSN
- 0013-936X
- eISSN
- 1520-5851
- Publisher
- United States
- Grant note
- P42 ES013661 / NIEHS NIH HHS P30 ES005605 / NIEHS NIH HHS R21 ES027169 / NIEHS NIH HHS
- Language
- English
- Date published
- 05/15/2018
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute; Iowa Superfund Research Program
- Record Identifier
- 9984000924802771
Metrics
27 Record Views