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Related Experiment Videos

Human exposures to mutagens--an analysis using the genetic activity profile database

R R Tice1, H F Stack, M D Waters

  • 1Integrated Laboratory Systems, Research Triangle Park, North Carolina, USA.

Environmental Health Perspectives
|May 1, 1996
PubMed
Summary

Humans show significantly higher sensitivity to genotoxic substances than rodents, based on Genetic Activity Profile (GAP) data. This highlights the need for robust protection against environmental mutagens.

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Area of Science:

  • Toxicology
  • Genetics
  • Environmental Health

Background:

  • The Genetic Activity Profile (GAP) database compiles data on agents with genotoxic activity.
  • Comparative analysis of human and rodent responses to genotoxic agents is crucial for risk assessment.

Purpose of the Study:

  • To identify and compare agents exhibiting genotoxic activity in humans using the GAP database.
  • To evaluate the comparative sensitivity of human and rodent cells to genotoxic substances.

Main Methods:

  • Utilized the Genetic Activity Profile (GAP) database for agent identification and comparison.
  • Analyzed cytogenetic data from both human and rodent studies.
  • Calculated the ratio of lowest effective doses (LEDs) between species for in vivo and in vitro studies.

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Main Results:

  • Humans appear at least 10 times more sensitive than rodents to most examined genotoxic substances in vivo.
  • In vitro studies showed less consistent differences in sensitivity between human and rodent cells compared to in vivo findings.
  • Caveats such as test protocol variations and inherent cellular differences may influence observed sensitivity disparities.

Conclusions:

  • Apparent higher human sensitivity to genotoxins in vivo warrants caution and further investigation into contributing factors.
  • In vitro data suggest that observed in vivo differences in sensitivity should be interpreted with caution.
  • Overall genotoxic profiles, especially human in vivo data, emphasize the necessity of protecting humans from environmental mutagens.