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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
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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.
Supplementary Notes Pub. in Toxicology and Applied Pharmacology, v82 n1 p175-179 Jan 86. Sponsored by Health Effects Research Lab., Research Triangle Park, NC.
NTIS Title Notes Journal article.
Title Annotations Reprint: Teratogen Metabolism: Thalidomide Activation is Mediated by Cytochrome P-450.
PUB Date Free Form c1986
Category Codes 6T; 57Y
NTIS Prices PC A02/MF A01
Primary Description 600/11
Document Type NT
Cataloging Source NTIS/MT
Control Number 622718371
Origin NTIS
Type CAT