| Main Title |
Teratogen Metabolism: Thalidomide Activation is Mediated by Cytochrome P-450. |
| Author |
Braun, A. G. ;
Harding, F. A. ;
Weinreb, S. L. ;
|
| CORP Author |
Massachusetts Inst. of Tech., Cambridge. Dept. of Applied Biological Sciences.;Health Effects Research Lab., Research Triangle Park, NC. |
| Year Published |
1986 |
| Report Number |
EPA/600/J-86/089; |
| Stock Number |
PB86-208527 |
| Additional Subjects |
Toxicology ;
Metabolism ;
Reprints ;
Thalidomide ;
Metabolites ;
Teratogenesis
|
| Holdings |
| Library |
Call Number |
Additional Info |
Location |
Last
Modified |
Checkout
Status |
| NTIS |
PB86-208527 |
Some EPA libraries have a fiche copy filed under the call number shown. |
|
07/26/2022 |
|
| Collation |
7p |
| Abstract |
A metabolite of thalidomide generated by hepatic microsomes inhibited the attachment of tumor cells to concanavalin A-coated polyethylene. Evidence that metabolite formation is mediated by microsomal cytochrome P-450 is presented. Microsomes incubated with thalidomide underwent a type I spectral shift. Metabolite formation was reduced or eliminated by carbon monoxide, SKF-525A, metyrapone, and N-octylamine. Superoxide dismutase treatment had no effect. Metabolite formation required microsomes and NADPH and was dependent on the length of 37 C incubation. The metabolite could be isolated by successive hexane and chloroform extractions. It is likely the inhibitory thalidomide metabolite was generated by a minor cytochrome P-450 species. Whether the thalidomide metabolite is involved in the drug's teratogenic activity remains to be shown. |
