| 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 |
Related Documents
:
|
19536577 - Characterization of mutant serine palmitoyltransferase 1 in ly-b cells. 17147977 - Mutagenicity of diesel exhaust particles mediated by cell-particle interaction in mamma... 3943137 - Potentiation of alkylation-induced sister chromatid exchange frequency by 3-aminobenzam... 1900747 - The chinese hamster cell mutant v-h4 is homologous to fanconi anemia (complementation g... 22707247 - Mitochondria in heart failure: the emerging role of mitochondrial dynamics. 6325027 - Bhk cell variant with defective fibronectin receptor function. |
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 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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
Previous Document: Preliminary communication: examination of the harmful effect to fetuses of fumonisin B(1) in pregnan...
Next Document: Increment of sister chromatid exchange frequencies (SCE) due to epichlorohydrin (ECH) in vitro treat...