Document Detail


SFTG international collaborative study on in vitro micronucleus test I. General conditions and overall conclusions of the study.
MedLine Citation:
PMID:  16815079     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study, coordinated by the SFTG (French branch of European Environmental Mutagen Society), included 38 participants from Europe, Japan and America. Clastogens (bleomycin, urethane), including base and nucleoside analogs (5-fluorouracil and cytosine arabinoside), aneugens and/or polyploidy inducers (colchicine, diethylstilboestrol, griseofulvin and thiabendazole), as well as non-genotoxic compounds (mannitol and clofibrate), were tested. Four cell types were used, i.e. human lymphocytes in the presence of cytochalasin B and CHO, CHL and L5178Y cell lines, in the presence or absence of cytochalasin B, with various treatment-recovery schedules. Mitomycin C was used as a positive control for all cell types. Mannitol and clofibrate were consistently negative in all cell types and with all treatment-recovery conditions. Urethane, known to induce questionable clastogenicity, was not found as positive. Bleomycin and mitomycin C were found positive in all treatment-recovery conditions. The base and nucleoside analogs were less easy to detect, especially 5-fluorouracil due to the interference with cytotoxicity, while cytosine arabinoside was detected in all cell types depending on the treatment-recovery schedule. Aneugens (colchicine, diethylstilboestrol and griseofulvin) were all detected in all cell types. In this study, the optimal detection was ensured when a short treatment followed by a long recovery was associated with a long continuous treatment without recovery. There was no impact of the presence or absence of cytochalasin B on the detection of micronucleated cells on cell lines. Scoring micronucleated cells in both mononucleated and binucleated cells when using cytochalasin B was confirmed to be useful for the detection and the identification of aneugens. In conclusion, these results, together with previously published validation studies, provide a useful contribution to the optimisation of a study protocol for the detection of both clastogens and aneugens in the in vitro micronucleus test.
Authors:
Elisabeth Lorge; Veronique Thybaud; Marilyn J Aardema; Jo Oliver; Akihiro Wakata; Giocondo Lorenzon; Daniel Marzin
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Publication Detail:
Type:  Evaluation Studies; In Vitro; Journal Article; Validation Studies     Date:  2006-06-30
Journal Detail:
Title:  Mutation research     Volume:  607     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-07-17     Completed Date:  2006-09-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  13-36     Citation Subset:  IM    
Affiliation:
Servier Group, Drug Safety Assessment, Orleans-Gidy, France. elisabeth.lorge@fr.netgrs.com
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MeSH Terms
Descriptor/Qualifier:
Aneugens / toxicity
Animals
Bleomycin / toxicity
CHO Cells
Cell Line
Clofibrate / toxicity
Colchicine / toxicity
Cricetinae
Cytarabine / toxicity
Cytochalasin B
Diethylstilbestrol / toxicity
Fluorouracil / toxicity
Griseofulvin / toxicity
Humans
International Cooperation
Leukemia L5178
Lymphocytes / drug effects
Mannitol / toxicity
Mice
Micronucleus Tests / methods*,  standards
Mitomycin / toxicity
Mutagens / toxicity
Thiabendazole / toxicity
Chemical
Reg. No./Substance:
0/Aneugens; 0/Mutagens; 11056-06-7/Bleomycin; 126-07-8/Griseofulvin; 147-94-4/Cytarabine; 148-79-8/Thiabendazole; 14930-96-2/Cytochalasin B; 50-07-7/Mitomycin; 51-21-8/Fluorouracil; 56-53-1/Diethylstilbestrol; 637-07-0/Clofibrate; 64-86-8/Colchicine; 69-65-8/Mannitol

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


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