Relationships between p53 status, apoptosis and induction of micronuclei in different human and mouse cell lines in vitro: Implications for improving existing assays

Publication date: Available online 30 May 2015 Source:Mutation Research/Genetic Toxicology and Environmental Mutagenesis Author(s): James Whitwell , Robert Smith , Karen Jenner , Heather Lyon , Deborah Wood , Julie Clements , Kelly Aschcroft-Hawley , Bhaskar Gollapudi , David Kirkland , Elisabeth Lorge , Stefan Pfuhler , Jennifer Y. Tanir , Veronique Thybaud Accumulated evidence has shown that in vitro mammalian cell genotoxicity assays produce high frequencies of “misleading” positive results, i.e. predicted hazard is not confirmed in in vivo and/or carcinogenicity studies [1], raising the question of relevance to human risk assessment. A recent study of micronucleus (MN) induction [2] showed that commonly used p53-deficient rodent cell lines (CHL, CHO and V79) gave a higher frequency of “misleading” positive results with 9 non-DNA reactive, Ames-negative and in vivo negative chemicals [3] than human p53-competent cells (blood lymphocytes, TK6 and HepG2 cell lines). This raised the question of whether these differences were due to p53 status or species origin. This present study compared human versus mouse and p53-competent versus p53-mutated function. The same 9 chemicals were tested for induction of MN in mouse lymphoma L5178Y (mutated p53), human TK6 (functional p53) and WIL2-NS (TK6 related, with mutated p53) cells. Six chemicals provided clear positive increases in MN frequency in at least one cell type. L5178Y cells yielded clear positive respo...
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research