Document Detail


Examination of a rodent limb bud micromass assay as a prescreen for developmental toxicity.
MedLine Citation:
PMID:  2326758     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mouse limb bud micromass assay is one of many short-term tests proposed as preliminary screens for potential developmental toxicity. Previous efforts to validate this assay have used too few "nonteratogens." The purpose of this study was to examine additional compounds, most of which, based on the literature, were perceived to have low potential for developmental toxicity in vivo. In addition, a method of data analysis was sought that would identify selective developmental toxins in the micromass assay, i.e., those that are effective at dosages not maternally toxic. The concentration of each of 23 compounds that produced a 50% inhibition (IC50) of radiolabeled thymidine (T) and sulfate (S) incorporation was determined and used to calculate a T/S ratio. The T/S ratio may be a useful measure of developmental hazard, since T incorporation measures toxicity toward a general cell function (DNA synthesis) and S incorporation measures mainly toxicity toward a developmentally specific cell activity (chondroitin sulfate synthesis). All compounds tested produced T/S ratios of less than 2.0. Since 22 of these 23 compounds are classified as "nonteratogens" or nonselective developmental toxins in vivo, a low T/S ratio in this in vitro assay system may be capable of discriminating potential for developmental hazard in vivo.
Authors:
L D Wise; R L Clark; J O Rundell; R T Robertson
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Teratology     Volume:  41     ISSN:  0040-3709     ISO Abbreviation:  Teratology     Publication Date:  1990 Mar 
Date Detail:
Created Date:  1990-05-21     Completed Date:  1990-05-21     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0153257     Medline TA:  Teratology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  341-51     Citation Subset:  IM    
Affiliation:
Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cells, Cultured
Drug Evaluation, Preclinical / methods
Female
Limb Deformities, Congenital*
Mice
Pregnancy
Teratogens*
Toxicology / methods*
Chemical
Reg. No./Substance:
0/Teratogens

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


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