Related Experiment Videos
Toxicity testing with animal viruses: I. Vaccinia virus growth as a model system for teratogens
1Department of Biological Sciences, University of Cincinnati, OH 45221.
Abstract:
A simple, rapid, inexpensive test for teratogens has been developed using vaccinia virus growth in primate cell cultures. Eighty-four percent of the test compounds that are known to produce teratogenesis in laboratory animals, prevented the formation of viable virus at dosages that did not cause any observable cytotoxicity to uninfected cells. The virus test had one false positive and 5 false negatives out of 74 test compounds. Moreover, the 50% inhibitory dose in vitro (RD50) was significantly correlated (p less than 0.001) with the in vivo, lowest reported teratogenic dose (LTD). The RD50 was not correlated with the in vivo lethal dose (LD50). Thus the virus test appears to be more sensitive to development than to general toxicity. A comparison of the in vitro RD50 with the in vivo, rodent LTD indicated that the two tests were equally predictive of human teratogenesis.
Insights
A new vaccinia virus test accurately identifies teratogens, chemicals causing birth defects. This rapid, inexpensive method shows high predictive value for human teratogenesis, distinguishing developmental toxicity from general toxicity.
Area of Science:
- Toxicology
- Developmental Biology
- Virology
Background:
- Teratogens are agents causing birth defects.
- Existing teratogen testing methods can be slow and expensive.
- A need exists for rapid, cost-effective teratogenicity screening.
Purpose of the Study:
- To develop and validate a simple, rapid, and inexpensive test for teratogens.
- To assess the correlation between in vitro and in vivo teratogenicity data.
- To evaluate the test's sensitivity to developmental toxicity versus general toxicity.
Main Methods:
- Utilized vaccinia virus growth inhibition in primate cell cultures as the assay.
- Tested 74 compounds, comparing in vitro results with known in vivo teratogenic and lethal doses.
- Calculated the 50% inhibitory dose in vitro (RD50) and correlated it with in vivo lowest reported teratogenic dose (LTD) and lethal dose (LD50).
Main Results:
- The vaccinia virus test correctly identified 84% of known teratogens.
- The test demonstrated a significant correlation between in vitro RD50 and in vivo LTD (p < 0.001).
- The RD50 did not correlate with the in vivo LD50, indicating specificity for developmental toxicity.
Conclusions:
- The vaccinia virus-based assay is a sensitive and predictive method for identifying teratogens.
- This in vitro test effectively distinguishes developmental toxicity from general cytotoxicity.
- The test shows comparable predictive value for human teratogenesis as in vivo rodent studies.