| The role of metabolism in determining susceptibility to parathion toxicity in man. | |
| | |
MedLine Citation:
|
PMID: 10414794 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Human liver microsomes (n = 16) activated parathion (O, O, diethyl O-p-nitrophenyl phosphorothioate, 20 and 200 microM) to paraoxon at a rate of 23.3-199.3 and 18.7-310.3 pmol/min per mg protein, respectively. p-Nitrophenol, was also formed, at 321.1-769.2 and 406.2-778.3 pmol/min per mg protein. This represented a 16-fold and 2-fold range in capacity to activate and detoxify parathion, respectively. Parathion was activated with an apparent Km of 9-16 microM (n = 3). The activation of parathion (200 microM) was positively correlated with nifedipine oxidation, indicating the involvement of CYP3A. Correlations were not significant with ethoxyresorufin-O-dealkylation (CYP1A1/2), pentoxyresorufin-O-dealkylation (CYP2B6), p-nitrophenol hydroxylation (CYP2E1), paraoxon hydrolysis (A-esterase) or phenylvalerate hydrolysis (B-esterase). Paraoxon formation from parathion was markedly reduced by CYP3A inhibitors. Experiments with EDTA indicated that A-esterase was not functionally important at low levels of paraoxon. Human P450s 3A4 and 3A5 expressed microsomes were the most efficient at biotransforming parathion to paraoxon, although P450s 1A1, 2B6 and 2C8 also catalysed the reaction. This study has determined wide interindividual variations in capacity to metabolise parathion, mainly by CYP3A, which may influence its manifest toxicity. |
| | |
Authors:
|
E Mutch; P G Blain; F M Williams |
Related Documents
:
|
6559114 - Biochemical mechanisms of resistance to insecticides. 21876374 - Molecular characterization of bile salt hydrolase from bifidobacterium animalis subsp. ... 20977394 - Inhibition of two enzyme systems in euchlanis dilatata (rotifera: monogononta) as bioma... 6704404 - Partial purification and characterization of a microsomal carboxylesterase specific for... 19745534 - A tyrosinase biosensor based on zno nanorod clusters/nanocrystalline diamond electrodes... 1515124 - Properties of phosphorylated protein intermediates of the bacterial phosphoenolpyruvate... |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Toxicology letters Volume: 107 ISSN: 0378-4274 ISO Abbreviation: Toxicol. Lett. Publication Date: 1999 Jun |
Date Detail:
|
Created Date: 1999-07-29 Completed Date: 1999-07-29 Revised Date: 2004-11-17 |
Medline Journal Info:
|
Nlm Unique ID: 7709027 Medline TA: Toxicol Lett Country: NETHERLANDS |
Other Details:
|
Languages: eng Pagination: 177-87 Citation Subset: IM |
Affiliation:
|
Department of Environmental and Occupational Medicine, The Medical School, Newcastle University, UK. elaine.mutch@ncl.ac.uk |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Cytochrome P-450 Enzyme System
/
physiology Edetic Acid / pharmacology Humans Insecticides / adverse effects* Microsomes, Liver / metabolism Nifedipine / metabolism Parathion / adverse effects*, metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Insecticides; 21829-25-4/Nifedipine; 56-38-2/Parathion; 60-00-4/Edetic Acid; 9035-51-2/Cytochrome P-450 Enzyme System |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Chronic sequelae and irreversible injuries following acute pyrethroid intoxication.
Next Document: Indoor air pollution by lindane and DDT indicated by head hair samples of children.