Document Detail

How accurate is in vitro prediction of carcinogenicity?
MedLine Citation:
PMID:  21091657     Owner:  NLM     Status:  MEDLINE    
Positive genetic toxicity data suggest carcinogenic hazard, and this can stop a candidate pharmaceutical reaching the clinic. However, during the last decade, it has become clear that many non-carcinogens produce misleading positive results in one or other of the regulatory genotoxicity assays. These doubtful conclusions cost a lot of time and money, as they trigger additional testing of apparently genotoxic candidates, both in vitro and in animals, to discover whether the suggested hazard is genuine. This in turn means that clinical trials can be put on hold. This review describes the current approaches to the 'misleading positive' problem as well as efforts to reduce the use of animals in genotoxicity assessment. The following issues are then addressed: the application of genotoxicity testing screens earlier in development; the search for new or improved in vitro genotoxicity tests; proposed changes to the International Committee on Harmonisation guidance on genotoxicity testing [S2(R1)]. Together, developments in all these areas offer good prospects of a more rapid and cost-effective way to understand genetic toxicity concerns.
Richard Maurice Walmsley; Nicholas Billinton
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  British journal of pharmacology     Volume:  162     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-23     Completed Date:  2011-09-06     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1250-8     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
University of Manchester, Manchester, UK.
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MeSH Terms
Carcinogenicity Tests*
DNA Damage
Drug Discovery*
Drug Evaluation, Preclinical
False Positive Reactions
Guidelines as Topic
Mutagenicity Tests*
Neoplasms / chemically induced
Reg. No./Substance:

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