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Evaluation of phenolphthalein, diazepam and quinacrine dihydrochloride in the in vitro mammalian cell micronucleus test in Chinese hamster ovary (CHO) and TK6 cells.
MedLine Citation:
PMID:  20399283     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
The in vitro micronucleus assay has been extensively used as an in vitro screening tool to identify test articles that might have aneugenic or clastogenic potential. Currently, the Organization for Economic Co-operation and Development (OECD) is working towards a final version of the guideline for the conduct of the in vitro mammalian cell micronucleus Test (MNvit). A few questions regarding appropriate cytotoxicity measurements and cytotoxicity limits to use remain to be answered. In order to resolve the remaining questions, we compared the induction of micronuclei at the top dose (50-60% cytotoxicity) determined by either Relative Cell Counts (RCC), Relative Increase in Cell Counts (RICC), Relative Population Doublings (RPD), or Cytokinesis-Blocked Proliferating Index (CBPI) using weak and strong inducers of micronuclei in both the presence and absence of cytochalasin B (CYB) in Chinese hamster ovary (CHO) and human lymphoblastoid TK6 cells. In order to assess extensive dose-response relationships, we selected expected weak (diazepam, phenolphthalein, quinacrine dihydrochloride dihydrate) and strong (cytosine arabinoside, mitomycin C, vinblastine sulphate) inducers of micronuclei with a variety of different mechanisms of action for testing. The results clearly demonstrated that all six compounds produced positive responses using either cytotoxicity measurement. The outcome from these studies further supports the cytotoxicity measurements and cytotoxicity limits proposed in the draft OECD guideline.
Authors:
Maik Schuler; Ramadevi Gudi; Jennifer Cheung; Shyam Kumar; Donna Dickinson; Maria Engel; Anna Szkudlinska; Megan Colman; Nkechi Maduka; Jocelyn Sherman; Catherine Thiffeault
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Publication Detail:
Type:  Journal Article     Date:  2010-04-21
Journal Detail:
Title:  Mutation research     Volume:  702     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2011-01-06     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  219-29     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
Affiliation:
Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. maik.schuler@pfizer.com
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