Document Detail


Assessment of the in vitro and in vivo genotoxicity of Thalomid (thalidomide).
MedLine Citation:
PMID:  10992277     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Thalomid is the FDA-approved commercial formulation of thalidomide currently used in the US to treat erythema nodosum leprosum, a complication of leprosy. The genotoxicity of Thalomid thalidomide was assessed in the Ames reverse mutation, AS52/XPRT mammalian cell forward gene mutation, and mouse bone marrow micronucleus assays. The Ames and AS52 assays were performed with and without S9. In the Ames, Salmonella typhimurium strains TA1535, 1537, 98, 100, and 102 and Escherichia coli strain WP2 uvrA were used. Assays were performed by using plate incorporation and liquid pre-incubation systems at thalidomide doses of 50-10,000 microg/plate. In the AS52 assay, Chinese hamster ovary cells were plated with fortified Ham's F12 medium and incubated overnight. The medium was then incubated with 1-1000 microg/ml thalidomide. After a series of aspirations, washings, reconstitutions, and incubations, mutant AS52 cells were fixed and stained. Colonies were then counted and the relative survival frequencies compared to negative controls. In the mouse micronucleus assay, Crl:CD-1 albino mice were dosed with 500, 2,500, and 5,000 mg/kg thalidomide and sacrificed over 72 h. Femurs were flushed with fetal bovine serum and the suspensions centrifuged. The supernatant was aspirated and the cell pellet resuspended and stained. Polychromatic erythrocytes were scored for micronucleated polychromatic and normochromatic erythrocytes. Thalidomide did not increase revertant frequencies in all bacterial strains. It also did not produce any significant increase in the average mutant frequencies of AS52 cells and mouse micronucleated polychromatic erythrocytes. We conclude that Celgene's Thalomid thalidomide is non-genotoxic.
Authors:
S Teo; M Morgan; D Stirling; S Thomas
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Teratogenesis, carcinogenesis, and mutagenesis     Volume:  20     ISSN:  0270-3211     ISO Abbreviation:  Teratog., Carcinog. Mutagen.     Publication Date:  2000  
Date Detail:
Created Date:  2000-10-17     Completed Date:  2000-10-30     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  8100917     Medline TA:  Teratog Carcinog Mutagen     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  301-11     Citation Subset:  IM    
Affiliation:
Celgene Corporation, Warren, New Jersey 07059, USA. Steo@celgene.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Marrow Cells / cytology,  drug effects*,  pathology
CHO Cells
Cell Survival / drug effects*
Cricetinae
Dimethylnitrosamine / toxicity
Escherichia coli / drug effects,  genetics
Ethyl Methanesulfonate / toxicity
Female
Male
Mice
Micronucleus Tests
Mutagenesis*
Mutagenicity Tests
Mutagens / pharmacology*,  toxicity
Salmonella typhimurium / drug effects,  genetics
Thalidomide / pharmacology*,  toxicity
Chemical
Reg. No./Substance:
0/Mutagens; 50-35-1/Thalidomide; 62-50-0/Ethyl Methanesulfonate; 62-75-9/Dimethylnitrosamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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