Structural analysis and predictive value of the rodent in vivo micronucleus assay results

Mutagenesis. 2010 Jul;25(4):335-41. doi: 10.1093/mutage/geq010. Epub 2010 Mar 1.

Abstract

In vivo genotoxicity studies-shortly followed by carcinogenicity-are posing high demand for test-related recourses in terms of animal lives and resources. Among those, the micronucleus test in rodents is the most widely used as a follow-up to positive in vitro mutagenicity results; therefore, the development and extensive use of estimation techniques based on the concept of Structure-Activity Relationships-such as (Quantitative) Structure-Activity Relationships, read-across and grouping of chemicals-might have a huge saving potential for this end point. In this paper, we present a newly derived compilation of Structural Alerts for the rodent in vivo micronucleus assay, thus providing a coarse-grain filter for preliminary screening of potentially in vivo mutagens. The compilation has been implemented as computerized rule of the expert system Toxtree and is freely available: http://ecb.jrc.ec.europa.eu/qsar/qsar-tools/index.php?c=TOXTREE. In addition, analyses on the performance of the micronucleus assay as pre-screening tool for carcinogenesis indicate that this assay is prone to give false-negative predictions and point to the need of improving the in vivo component of the present testing schemes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogens / toxicity*
  • DNA Damage
  • Micronuclei, Chromosome-Defective / chemically induced
  • Micronucleus Tests*
  • Mutagenicity Tests
  • Mutagens / toxicity*
  • Neoplasms / chemically induced
  • Quantitative Structure-Activity Relationship
  • Rodentia

Substances

  • Carcinogens
  • Mutagens