The Chicken Egg Genotoxicity Assay (CEGA): Assessing Target Tissue
Exposure and Metabolism in the Embryo-Fetal Chicken Livers
Abstract
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The Chicken Egg Genotoxicity Assay (CEGA) is an avian egg-based model
that utilizes the livers of developing chicken embryo-fetuses to assess
the ability of chemicals to produce direct DNA damage. The main goal of
the study was to evaluate target tissue exposure and metabolism in the
CEGA to assess its suitability as a biologically relevant new approach
methodology (NAM) for detecting genotoxic potential of chemicals. An
imaging study using two-photon excitation microscopy following
administration of a fluorescent dye (acridine orange) verified that
chemicals following administration into the air sac of the fertilized
chicken egg reach the target organ, liver. Additionally, a metabolism
study using liquid chromatography with high resolution mass spectrometry
(LC/MS), conducted after administration of benzo[a]pyrene (B(a)P)
according to the CEGA protocol, confirmed the formation of sufficient
amounts of reactive metabolite(s) responsible for genotoxic effects of a
parent compound upon reaching the target tissue. Moreover, RNA
sequencing study revealed that B(a)P in embryo-fetal chicken livers
significantly upregulated several genes responsible for the activity of
CYP1A1 enzyme which is critical for bioactivation of B(a)P. These
findings support previous reports in CEGA, where B(a)P produced DNA
damage in the liver tissues in the form of strand breaks and adducts.
Overall, the findings in the study support the conclusion that the CEGA
can be considered a robust potential alternative to animal testing
strategy for assessing the genotoxic potential of chemicals