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Segregation of molecular mechanisms of genotoxicity and carcinogenicity across human, yeast and Salmonella species

22 February 2010  •  Author(s):

Screening assays for in vitro toxicity are the way to reduce the attrition rates in the preclinical development of new drugs. Here a test battery is presented for screening of genotoxic and carcinogenic compounds by means of VitotoxTM, RadarScreen, and four human liver HepG2 cell lines with two different promoters as well as responsive element (RE) settings in combination with a luminescent read-out. The VitotoxTM assay in Salmonella is a substitute for the Ames test and the RadarScreen assay for in vitro clastogenicity. Moreover, HepG2 assays with RAD51C and Cystatin A promoters, and p53-RE are more predictive for in vivo clastogenicity. The Nrf2-RE can be used for analysis of reactive oxygen species production. The validity of this battery is checked for 62 compounds of an ECVAM list for genotoxicity and for 190 other references or in house drugs.

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