Abstract:
INTRODUCTION:In vitro genotoxicity assays have a high sensitivity to detect rodent carcinogens, but mammalian cell tests have a propensity for misleading positive results (poor specificity). Recent data show a greater risk of misleading positive results in p53-deficient rodent cell lines than in p53-competent human cells. Measures of cytotoxicity, source and stability of cells used are also important. AREAS COVERED:In this review, potential reduction in the top concentration for testing (10 mM) is discussed. Indirect effects on non-DNA targets, which may not be relevant for humans or may exhibit a threshold, have been identified. EXPERT OPINION:The reliability of in vitro genotoxicity tests could be improved by selecting p53-proficient, human cells. The provenance and stability of the cells used should be demonstrated. Measures of cytotoxicity based on cell proliferation should be used. Lowering the top concentration for testing from 10 mM to 4 mM or 2000 μg/ml, whichever is the lower, as proposed by some experts, would seem to be justified. Artefacts that may be caused by reaction of test substance with culture medium should be avoided. Better understanding and investigation of the potential for threshold and irrelevant modes of action are encouraged.
journal_name
Expert Opin Drug Metab Toxicoljournal_title
Expert opinion on drug metabolism & toxicologyauthors
Kirkland Ddoi
10.1517/17425255.2011.627855subject
Has Abstractpub_date
2011-12-01 00:00:00pages
1513-20issue
12eissn
1742-5255issn
1744-7607journal_volume
7pub_type
杂志文章,评审abstract:INTRODUCTION:Obesity is an epidemic associated with significant morbidity. Lorcaserin , a novel serotonin 2C receptor antagonist, was recently approved as an adjunct to lifestyle modification for long-term weight loss and maintenance. Clinical studies in patients without diabetes demonstrated 5.8% mean weight loss from...
journal_title:Expert opinion on drug metabolism & toxicology
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doi:10.1517/17425255.2013.798643
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journal_title:Expert opinion on drug metabolism & toxicology
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journal_title:Expert opinion on drug metabolism & toxicology
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journal_title:Expert opinion on drug metabolism & toxicology
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