Empirical comparison of genotoxic potency estimations: the in vitro DNA-damage ToxTracker endpoints versus the in vivo micronucleus assay.

Mutagenesis
John W WillsGeorge E Johnson

Abstract

Genetic toxicology is an essential component of compound safety assessment. In the face of a barrage of new compounds, higher throughput, less ethically divisive in vitro approaches capable of effective, human-relevant hazard identification and prioritisation are increasingly important. One such approach is the ToxTracker assay, which utilises murine stem cell lines equipped with green fluorescent protein (GFP)-reporter gene constructs that each inform on distinct aspects of cellular perturbation. Encouragingly, ToxTracker has shown improved sensitivity and specificity for the detection of known in vivo genotoxicants when compared to existing 'standard battery' in vitro tests. At the current time however, quantitative genotoxic potency correlations between ToxTracker and well-recognised in vivo tests are not yet available. Here we use dose-response data from the three DNA-damage-focused ToxTracker endpoints and from the in vivo micronucleus assay to carry out quantitative, genotoxic potency estimations for a range of aromatic amine and alkylating agents using the benchmark dose (BMD) approach. This strategy, using both the exponential and the Hill BMD model families, was found to produce robust, visually intuitive and similarly...Continue Reading

References

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Oct 8, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Lya G Soeteman-HernándezWout Slob
Jan 1, 2016·Toxicological Sciences : an Official Journal of the Society of Toxicology·Giel HendriksHarry Vrieling
Aug 10, 2018·Toxicology Research·Jay I Goodman

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