Document Detail


Hormesis predicts low-dose responses better than threshold models.
MedLine Citation:
PMID:  19037807     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
This study evaluated characteristics of the concentration-response relationships of chemicals from the U.S. National Cancer Institute (NCI) Yeast Anticancer Drug Screen database with respect to the threshold and the hormetic dose-response models. The database reported concentration-response studies of 2189 chemicals from a broad range of chemical classes. The biological end point was growth in 13 strains of yeast (Saccharomyces cerevisiae), most of which contain genetic alterations affecting DNA repair or cell cycle control. The analysis was limited to studies that satisfied a priori entry criteria for evaluation, including having two or more concentrations in the nontoxic zone (below a Benchmark Dose). The mean growth response compared to untreated controls of these doses was significantly greater than 100% in all 13 yeast strains, ranging from approximately 105% to approximately 111%. Under a threshold model, one would expect values more closely approximating 100%. Moreover, the distribution of responses below the BMD5 for chemicals was shifted upwardly from the expectations of a threshold model for all strains. These results indicate that for the chemicals and yeast strains studied, the responses are more consistent with a hormetic model than a threshold model, and they strengthen previous results presented by Calabrese et al. (2006, Toxicol. Sci. 94:368-378). Taken together, the analyses provide strong evidence for hormesis, a phenomenon with a broad range of biomedical and toxicological implications.
Authors:
Edward J Calabrese; Edward J Stanek; Marc A Nascarella; George R Hoffmann
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  International journal of toxicology     Volume:  27     ISSN:  1092-874X     ISO Abbreviation:  Int. J. Toxicol.     Publication Date:    2008 Sep-Oct
Date Detail:
Created Date:  2008-11-27     Completed Date:  2009-01-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9708436     Medline TA:  Int J Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  369-78     Citation Subset:  IM    
Affiliation:
Department of Public Health, Environmental Health Sciences Division, University of Massachusetts, Amherst, Massachusetts 01003, USA. edwardc@schoolph.umass.edu
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / chemistry,  toxicity
Benchmarking
Databases, Factual
Dose-Response Relationship, Drug*
Models, Biological*
Predictive Value of Tests
Saccharomyces cerevisiae / drug effects*,  genetics,  growth & development
Threshold Limit Values*
Toxicity Tests* / methods,  statistics & numerical data
Chemical
Reg. No./Substance:
0/Antineoplastic Agents

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


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