The Use of lacI Transgenic Mice in Genetic Toxicology

  • Johan G. de Boer
  • Heather L. Erfle
  • David Walsh
  • James Holcroft
  • Barry W. Glickman

Abstract

Exposure to genotoxic agents can have a significant impact on human health. In each country, regulatory agencies have been created to establish safeguards to protect the public by minimizing these risks, usually by reducing or eliminating exposures. When this is not possible, estimates are required to quantitate risks so that a risk-benefit analysis is possible. To estimate risk, the field of genetic toxicology has embraced a number of assay systems to evaluate the genetic toxicity. Most well known is the Ames/Salmonella test, which uses a series of tester strains, with and without addition of metabolic activating S9 liver microsome extracts. This assay is generally considered to be the backbone of what has become known as “Tier One” testing and is used to screen all new chemicals and pharmaceuticals that may be introduced into the environment. The Ames assay is usually the first attempt to determine mutagenic potential (Maron and Ames, 1983). Cytogenetic toxicity is also evaluated using mammalian systems, such as the mouse lymphoma in vitro assay (MLA) (Oberly et al., 1984; Hozier et al., 1981), the micronucleus test (MN) (Wild, 1978), and chromosomal aberrations (CA) and sister chromatid exchange assay (SCE) (Latt, 1974). Damage to the germ line can be assessed in rodents by the specific locus test (Russell and Russell, 1992; Russell et al., 1981). Carcinogenic potential can be determined in the National Toxicology Program assay (Chhabra et al., 1990), a 2-year-long exposure of mice or rats to the potential carcinogen, a costly and time-consuming exercise that requires large numbers of animals.

Keywords

Transgenic Mouse Mutant Frequency Spontaneous Mutation Mutational Spectrum lacZ Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Johan G. de Boer
    • 1
  • Heather L. Erfle
    • 1
  • David Walsh
    • 1
  • James Holcroft
    • 1
  • Barry W. Glickman
    • 1
  1. 1.Center for Environmental Health, Department of BiologyUniversity of VictoriaVictoriaCanada

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