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Prediction of chemical carcinogenicity in rodents from in vitro genetic toxicity assays
Abstract:
Four widely used in vitro assays for genetic toxicity were evaluated for their ability to predict the carcinogenicity of selected chemicals in rodents. These assays were mutagenesis in Salmonella and mouse lymphoma cells and chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells. Seventy-three chemicals recently tested in 2-year carcinogenicity studies conducted by the National Cancer Institute and the National Toxicology Program were used in this evaluation. Test results from the four in vitro assays did not show significant differences in individual concordance with the rodent carcinogenicity results; the concordance of each assay was approximately 60 percent. Within the limits of this study there was no evidence of complementarity among the four assays, and no battery of tests constructed from these assays improved substantially on the overall performance of the Salmonella assay. The in vitro assays which represented a range of three cell types and four end points did show substantial agreement among themselves, indicating that chemicals positive in one in vitro assay tended to be positive in the other in vitro assays.
Insights
Four in vitro genetic toxicity assays showed about 60% concordance in predicting rodent carcinogenicity. No combination of these assays significantly improved prediction accuracy over the Salmonella assay alone.
Area of Science:
- Toxicology
- Genetics
- Carcinogenesis
Background:
- In vitro assays are crucial for assessing chemical genotoxicity.
- Predicting rodent carcinogenicity from in vitro data is a key challenge in toxicology.
Purpose of the Study:
- To evaluate the predictive accuracy of four widely used in vitro genotoxicity assays for rodent carcinogenicity.
- To assess the complementarity and potential for a combined battery of these assays.
Main Methods:
- Evaluated four in vitro assays: Salmonella mutagenesis, mouse lymphoma cell mutagenesis, Chinese hamster ovary cell chromosome aberrations, and sister chromatid exchanges.
- Used 73 chemicals with existing 2-year rodent carcinogenicity study results from the National Cancer Institute and National Toxicology Program.
Main Results:
- Individual assay concordance with rodent carcinogenicity was approximately 60%, with no significant differences between the four assays.
- No evidence of complementarity was found among the assays; a battery did not substantially improve upon the Salmonella assay's performance.
- Substantial agreement was observed among the in vitro assays themselves, suggesting cross-validation of positive results.
Conclusions:
- The evaluated in vitro genotoxicity assays demonstrate moderate, but similar, predictive ability for rodent carcinogenicity.
- Current in vitro assay combinations do not offer significant improvement over single assays for predicting carcinogenicity.
- Further research may be needed to enhance the predictive power of in vitro genotoxicity testing for carcinogenicity assessment.