Loading...
Please wait, while we are loading the content...
Similar Documents
Antiandrogenic activity and metabolism of the organophosphorus pesticide fenthion and related compounds.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kitamura, Shigeyuki Suzuki, Tomoharu Ohta, Shigeru Fujimoto, Nariaki |
| Copyright Year | 2003 |
| Abstract | We investigated the endocrine-disrupting actions of the organophosphorus pesticide fenthion and related compounds and the influence of metabolic transformation on the activities of these compounds. Fenthion acted as an antagonist of the androgenic activity of dihydrotestosterone (10(-7)M) in the concentration range of 10(-6)-10(-4)M in an androgen-responsive element-luciferase reporter-responsive assay using NIH3T3 cells. The antiandrogenic activity of fenthion was similar in magnitude to that of flutamide. Fenthion also tested positive in the Hershberger assay using castrated male rats. Marked estrogenic and antiestrogenic activities of fenthion and related compounds were not observed in MCF-7 cells. When fenthion was incubated with rat liver microsomes in the presence of NADPH, the antiandrogenic activity markedly decreased, and fenthion sulfoxide was detected as a major metabolite. The oxidase activity toward fenthion was exhibited by cytochrome P450 and flavin-containing monooxygenase. Fenthion sulfoxide was negative in the screening test for antiandrogens, as was fenthion sulfone. However, when fenthion sulfoxide was incubated with liver cytosol in the presence of 2-hydroxypyrimidine, an electron donor of aldehyde oxidase, the extract of the incubation mixture exhibited antiandrogenic activity. In this case, fenthion was detected as a major metabolite of the sulfoxide. Metabolic interconversion between fenthion and fenthion sulfoxide in the body seems to maintain the antiandrogenic activity. |
| Starting Page | 503 |
| Ending Page | 508 |
| Page Count | 6 |
| File Format | PDF HTM / HTML |
| PubMed reference number | 12676606 |
| Volume Number | 111 |
| Journal | Environmental health perspectives |
| Alternate Webpage(s) | https://pdfs.semanticscholar.org/16f8/21bafe34ad7a3fae9a9af44ca6cc7c25a556.pdf |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 2-hydroxypyrimidine 4,6-dinitro-o-cresol Acetaldehyde Aldehyde oxidase Androgen Antagonists Androgens Dapsone Dihydrotestosterone Estrogen Antagonists Fenthion Flutamide Luciferases Metabolic Process, Cellular Methionine sulfoxide/Creatinine:SRto:24H:Urine:Qn Methionine sulfoxide:SRat:24H:Urine:Qn Microsomes Microsomes, Liver Mixed Function Oxygenases Organophosphates Pesticides Sulfones Sulfoxides incubated |
| Content Type | Text |
| Resource Type | Article |
