Abstract
We compared the ability of two clonally derived murine preadipocyte cell lines, 3T3-L1(L1) and 3T3-F442A (F442A), to differentiate after treatment by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and found that the former cell line was clearly suppressed by TCDD but the latter was not. It was initially postulated that the easiest way to explain the lack of response to TCDD in F442A cells could be an alteration in aryl hydrocarbon receptor (AhR) functionality. This hypothesis was tested first, but no differences were found in the levels or functions of AhR. To find an alternate explanation for such a differential effect of TCDD, we tested the action of several diagnostic agents on the process of adipocyte differentiation of these two cells. No differences were found between these two lines of cells in the susceptibility to the antiadipogenic action of 12-0-tetradecanoylphorbol-13-acetate (TPA), or to TNFα, indicating that the basic biochemical components engaged in the antiadipogenic actions of these agents in these two cell lines are similar. In contrast, F442A cells were found to be more resistant to the antiadipogenic action of EGF or TGFβ than L1 cells which were tested side by side. Based on the knowledge that TNFα preferentially affects C/EBPα and that TGFα specifically controls C/EBPβ and δ in their antiadipogenic action, we hypothesized that the major cause for the differential response of these two similar cell lines could be the insensitivity of C/EBPβ and/or δ of F442A cells to the action of TCDD. We could obtain supporting data for this hypothesis, showing that in F442A cells, the level of C/EBPβ is already high even before the addition of adipocyte differentiation factors and that TCDD did not cause any significant changes in the titer of C/EBPβ.
Original language | English (US) |
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Pages (from-to) | 70-83 |
Number of pages | 14 |
Journal | Journal of Biochemical and Molecular Toxicology |
Volume | 16 |
Issue number | 2 |
DOIs | |
State | Published - 2002 |
Keywords
- 3T3-L1 vs. F442A
- Difference in C/EBPβ
- Differential action of TCDD
- Inhibition of adipocyte differentiation
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Toxicology
- Health, Toxicology and Mutagenesis