New molecular endpoints and methods for routine toxicity testing

J. T. MacGregor, S. Farr, J. D. Tucker, J. A. Heddle, R. R. Tice, K. W. Turteltaub

Research output: Contribution to journalArticle

Abstract

New molecular and instrumental techniques have made available many markers of cellular damage that can be evaluated in multiple tissues in vivo at low cost without compromising the normal conduct of in vivo toxicity evaluations, and without the need for substitution of new species or strains of animals. These techniques include (1) the activation of stress genes that respond to general classes of toxic agents and cellular damage at doses below those that cause frank toxicity; (2) electrophoretic methods for the detection of DNA strand breakage due to DNA degradation resulting from cell death or genotoxic damage; (3) the use of fluorescent chromosome-specific DNA probes that allow evaluation of stable chromosomal rearrangements, chromosomal breaks, and aneuploidy in laboratory animals; and (4) endogenous and exogenous (transgenic) reporter genes for the evaluation of in vivo gene mutation. Additionally, powerful new analytical techniques such as accelerator mass spectrometry make possible ultrasensitive measurements of metabolite binding to specific macromolecular targets and permit pharmacokinetics studies at very low doses. Often, identical or analogous endpoints can be measured in cellular models, in laboratory animals, and in humans, an approach that allows in vitro screening for product development, in vivo hazard identification, and early risk assessments in animal models and direct risk assessment in humans. These new in vivo techniques will greatly enhance our ability to extrapolate laboratory data to human health risk.

Original languageEnglish (US)
Pages (from-to)156-173
Number of pages18
JournalFundamental and Applied Toxicology
Volume26
Issue number2
DOIs
StatePublished - 1995
Externally publishedYes

Fingerprint

Toxicity
Animals
Genes
Testing
Animal Models
Risk assessment
Chromosome Breakage
Poisons
DNA
DNA Probes
Laboratory Animals
Aneuploidy
Reporter Genes
Transcriptional Activation
Pharmacokinetics
Health risks
Mass Spectrometry
Cell Death
Cell death
Chromosomes

ASJC Scopus subject areas

  • Toxicology

Cite this

New molecular endpoints and methods for routine toxicity testing. / MacGregor, J. T.; Farr, S.; Tucker, J. D.; Heddle, J. A.; Tice, R. R.; Turteltaub, K. W.

In: Fundamental and Applied Toxicology, Vol. 26, No. 2, 1995, p. 156-173.

Research output: Contribution to journalArticle

MacGregor, J. T. ; Farr, S. ; Tucker, J. D. ; Heddle, J. A. ; Tice, R. R. ; Turteltaub, K. W. / New molecular endpoints and methods for routine toxicity testing. In: Fundamental and Applied Toxicology. 1995 ; Vol. 26, No. 2. pp. 156-173.
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