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Assessing the efficacy of an Aroclor 1254-induced exogenous metabolic activation system for FETAX
D J Fort1, J R Rayburn, D J DeYoung
1Department of Zoology, Oklahoma State University, Stillwater 74078.
Abstract:
The developmental toxicity of N-nitrosodimethylamine (NDMA) and trichloroethylene (TCE) was assessed with Frog Embryo Teratogenesis Assay: Xenopus (FETAX). Late Xenopus laevis blastulae were exposed to NDMA and TCE for 96-h in two separate static-renewal tests with and without the presence of three differently induced exogenous metabolic activation systems (MAS). The MAS consisted of Aroclor 1254-induced (Aroclor 1254 MAS), isoniazid-induced (INH MAS), and a post-isolation mixture (mixed MAS) of Aroclor 1254- and isoniazid-induced rat liver microsomes. Addition of the INH MAS and the mixed MAS increased the Teratogenic Index [TI = LC50/EC50 (malformation)] of NDMA and TCE nearly 2.0- and 2.1-fold and 2.1- and 1.7-fold, respectively. Inclusion of the Aroclor 1254 MAS did not alter the developmental toxicity of either compound. Based on TI values, embryo growth, and types and severity of induced malformations, both NDMA and TCE were developmentally toxic. Use of post-microsome isolation mixtures from differentially induced rat livers increased the efficacy of the exogenous MAS routinely used by FETAX.
Insights
N-nitrosodimethylamine (NDMA) and trichloroethylene (TCE) show developmental toxicity in Xenopus embryos. Specific metabolic activation systems enhanced their toxicity, improving the Frog Embryo Teratogenesis Assay: Xenopus (FETAX) efficacy.
Area of Science:
- Environmental toxicology
- Developmental toxicology
- Amphibian toxicology
Background:
- N-nitrosodimethylamine (NDMA) and trichloroethylene (TCE) are environmental contaminants with known toxicity.
- Assessing developmental toxicity is crucial for understanding risks to aquatic organisms.
- The Frog Embryo Teratogenesis Assay: Xenopus (FETAX) is a standard method for evaluating teratogenicity.
Purpose of the Study:
- To evaluate the developmental toxicity of NDMA and TCE using FETAX.
- To investigate the effect of different exogenous metabolic activation systems (MAS) on the toxicity of NDMA and TCE.
- To determine if modified MAS can enhance the sensitivity of the FETAX assay.
Main Methods:
- Xenopus laevis embryos were exposed to NDMA and TCE for 96 hours in static-renewal tests.
- Three types of MAS were used: Aroclor 1254-induced, isoniazid-induced (INH MAS), and a mixed MAS.
- Teratogenic Index (TI), embryo growth, and malformation types/severity were assessed.
Main Results:
- Both NDMA and TCE demonstrated developmental toxicity, causing malformations in Xenopus embryos.
- The INH MAS and mixed MAS significantly increased the Teratogenic Index (TI) of NDMA and TCE.
- Aroclor 1254 MAS did not alter the developmental toxicity of either compound.
- Modified MAS improved the efficacy of the exogenous MAS typically used in FETAX.
Conclusions:
- NDMA and TCE are confirmed developmental toxicants in the FETAX model.
- Exogenous metabolic activation systems, particularly those involving isoniazid, can enhance the detection of developmental toxicity.
- The study highlights the potential for optimizing FETAX with modified MAS for improved assessment of chemical teratogenicity.