Use of human derived liver cells for the detection of genotoxins in comet assays

Publication date: Available online 10 December 2018Source: Mutation Research/Genetic Toxicology and Environmental MutagenesisAuthor(s): Miroslav Mišík, Armen Nersesyan, Nathalie Ropek, Wolfgang W Huber, Elisabeth Haslinger, Siegfried KnasmuellerAbstractOne of the problems of in vitro genotoxicity testing is the inadequate representation of drug metabolizing enzymes in indicator cells which are currently used. An alternative is the use of human derived liver cells lines which retained the activities of enzymes that catalyze the activation and detoxification of genotoxins. Several cell lines were identified which were used in comet experiments. The most frequently employed line is HepG2, i.e. more than 400 individual compounds have been tested; furthermore, it was also used for the detection of combined effects in mixtures as drug metabolizing and antioxidant enzymes are represented in inducible form. One of the shortcomings of these cells is the strong inter-laboratory variations. Recently it was postulated that HepaRG cells are an ideal model for human liver studies, but comet experiments were only partly successful and failed to detect genotoxins such as cadmium chloride, styrene and etoposide, as well as compounds that require activation via N-actetyltransferases (IQ, 2,4-DAT, 2-AAF). Furthermore, these cells are relatively insensitive towards ROS. Hep3B cells were used in a few studies but failed to detect representatives of important genotoxic carcinogns (AFB1, B(a)P, N...
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research