Related Experiment Video
Updated: Jul 6, 2026
Administration of Δ9-Tetrahydrocannabinol (THC) in Adolescent and Adult Mice
Published on: August 1, 2025
Comparative temporal toxicogenomic analysis of TCDD- and TCDF-mediated hepatic effects in immature female C57BL/6
Alhaji N'Jai1, Darrell R Boverhof, Edward Dere
1Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, Michigan 48824, USA.
Abstract:
Temporal analyses were performed on hepatic tissue from immature female C57BL/6 mice in order to compare the gene expression profiles for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,3,7,8-tetrachlorodibzofuran (TCDF). Time course studies conducted with a single oral dose of 300 microg/kg TCDF or 30 microg/kg TCDD were used to compare differential gene expression on complementary DNA microarrays containing 13,361 features, representing 8194 genes at 2, 4, 8, 12, 24, 72, 120, and 168 h. One hundred and ninety-five genes were identified as differentially regulated by TCDF, of which 116 genes were in common with TCDD, with 109 exhibiting comparable expression profiles (correlation coefficients > 0.3). In general, TCDF was less effective in eliciting hepatic vacuolization, and differential gene expression compared with TCDD when given at an equipotent dose based on a toxic equivalence factor (TEF) of 0.1 for TCDF, especially 72-h postadministration. For example, the induction of Cyp1a1 messenger RNA by TCDF was less when compared TCDD. Moreover, TCDF induced less severe hepatocyte cytoplasmic vacuolization consistent with lower lipid accumulations which significantly subsided by 120 and 168 h when compared with TCDD. TCDF-elicited responses correlated with their hepatic tissue levels which gradually decreased between 18 and 168 h. Although both compounds elicited comparable gene expression profiles, especially at early time points, the TCDF responses were generally weaker. Collectively, these results suggest that the weaker TCDF responses could be attributed to differences in pharmacokinetics. However, more comprehensive dose-response studies are required at optimal times for each end point of interest in order to investigate the effect of pharmacokinetic differences on relative potencies that are important in establishing TEFs.
Insights
This study compared gene expression in mice exposed to TCDD and TCDF. While both dioxins affected gene expression, TCDF generally elicited weaker responses, possibly due to pharmacokinetic differences.
Area of Science:
- Toxicology
- Molecular Biology
- Environmental Health
Background:
- 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,3,7,8-tetrachlorodibzofuran (TCDF) are environmental contaminants with known toxic effects.
- Understanding their differential impacts on gene expression is crucial for risk assessment.
Purpose of the Study:
- To compare the temporal gene expression profiles induced by TCDD and TCDF in mouse hepatic tissue.
- To investigate potential pharmacokinetic influences on the relative potencies of TCDD and TCDF.
Main Methods:
- Immature female C57BL/6 mice were administered single oral doses of TCDF or TCDD.
- Hepatic tissue was analyzed over time (2-168 hours) using complementary DNA microarrays (13,361 features, 8194 genes).
- Gene expression data and histopathological changes (vacuolization, lipid accumulation) were assessed.
Main Results:
- 195 genes were differentially regulated by TCDF, with 116 common to TCDD.
- TCDF induced weaker hepatic vacuolization and lower lipid accumulation compared to TCDD, especially at 72 hours.
- Cyp1a1 mRNA induction was lower for TCDF than TCDD.
- TCDF responses generally correlated with hepatic tissue levels, which decreased over time.
Conclusions:
- Both TCDD and TCDF induced comparable gene expression profiles, particularly at early time points.
- TCDF generally elicited weaker toxic responses than TCDD, suggesting pharmacokinetic differences may play a role.
- Further dose-response studies are needed to clarify pharmacokinetic effects on relative potencies for TEF establishment.
