ArticleXenobiotica; the fate of foreign compounds in biological systems2012
Bioactivation of chlorpyrifos by CYP2B6 variants.
Article in Xenobiotica; the fate of foreign compounds in biological systems, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 18 citations in OpenAlex.
- Agrochemical residues and food safety: In-depth in silico assessment of the degradation mechanism of chlorpyrifos-oxon by niobium dioxide (NbO₂), a naturally occurring and cost-effective mineral.Journal of molecular modeling · 2026Article
- Concentration-dependent effects of chlorpyrifos oxon on peroxisome proliferator-activated receptor signaling in MCF-7 cells.Toxicology in vitro : an international journal published in association with BIBRA · 2022Article
- Human Family 1-4 cytochrome P450 enzymes involved in the metabolic activation of xenobiotic and physiological chemicals: an update.Archives of toxicology · 2021Review
- The Organophosphorus Pesticide Chlorpyrifos Induces Sex-Specific Airway Hyperreactivity in Adult Rats.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Halogen-π Interactions in the Cytochrome P450 Active Site: Structural Insights into Human CYP2B6 Substrate Selectivity.ACS chemical biology · 2017Article
- Cytochrome p450 mRNA expression in the rodent brain: species-, sex-, and region-dependent differences.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- Metabolism of profenofos to 4-bromo-2-chlorophenol, a specific and sensitive exposure biomarker.Toxicology · 2013Article
- Pharmacogenetics of cytochrome P450 2B6 (CYP2B6): advances on polymorphisms, mechanisms, and clinical relevance.Frontiers in genetics · 2013Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Chlorpyrifos (CPF), an organophosphorus (OP) pesticide, is bioactivated by cytochrome P450s (CYPs) to the active metabolite chlorpyrifos oxon (CPF-O). Given that human CYP2B6 has the highest intrinsic clearance (CL(int)) for CPF bioactivation, CYP2B6 polymorphisms may impact human susceptibility to CPF at real world environmental and occupational CPF exposure levels. CYP2B6.4,.5,.7, and .18 were over-expressed in mammalian COS-1 cells to assess the impact of CYP2B6 variants on the K(m) and V(max) for bioactivation of CPF. Cell lysates were incubated with CPF (0-100 μM) and the production of CPF-O was measured via HPLC analysis. CYP2B6 content was determined by western blot. CYP2B6.18 had neither detectable protein nor activity levels. The V(max) value for each remaining variant was significantly higher than wild-type (CYP2B6.1, V(max) 4.13 × 10(4) pmol/min/nmol CYP2B6), with CYP2B6.4,.5, and .7 having V(max) values of 4.52 × 10(5), 1.82 × 10(5), and 9.60 × 10(4) pmol/min/nmol CYP2B6, respectively. The K(m) values for these variants ranged from 0.39 to 1.09 μM and were not significantly different from wild-type. All active variants examined had significantly higher CL(int) than CYP2B6.1. Variants of CYP2B6 have altered capacity to bioactivate CPF and may affect individual susceptibility by altering the V(max) for CPF-O formation.
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Registered trials
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.