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Targets for dioxin: genes for plasminogen activator inhibitor-2 and interleukin-1 beta
T R Sutter1, K Guzman, K M Dold
1Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709.
Abstract:
Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD), a widespread environmental contaminant, may elicit its effects by altering gene expression in susceptible cells. Five TCDD-responsive complementary DNA clones were isolated from a human keratinocyte cell line. One of these clones encodes plasminogen activator inhibitor-2, a factor that influences growth and differentiation by regulating proteolysis of the extracellular matrix. Another encodes the cytokine interleukin-1 beta. Thus, TCDD alters the expression of growth regulatory genes and has effects similar to those of other tumor-promoting agents that affect both inflammation and differentiation.
Insights
Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) exposure alters gene expression in human cells. This environmental contaminant affects growth regulation and inflammation, similar to tumor promoters.
Area of Science:
- Environmental Science
- Molecular Biology
- Toxicology
Background:
- Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) is a pervasive environmental contaminant.
- TCDD is known to influence cellular processes, potentially through gene expression modulation.
Purpose of the Study:
- To identify specific genes regulated by TCDD in human cells.
- To understand the molecular mechanisms underlying TCDD's effects on cell growth and differentiation.
Main Methods:
- Isolation of complementary DNA (cDNA) clones from a human keratinocyte cell line exposed to TCDD.
- Analysis of the function of identified TCDD-responsive genes.
Main Results:
- Five TCDD-responsive cDNA clones were successfully isolated.
- One clone identified as encoding plasminogen activator inhibitor-2, a key regulator of extracellular matrix proteolysis.
- Another clone identified as encoding the cytokine interleukin-1 beta.
Conclusions:
- TCDD exposure significantly alters the expression of critical growth regulatory genes in human keratinocytes.
- The identified genes (plasminogen activator inhibitor-2 and interleukin-1 beta) suggest TCDD's role in processes involving inflammation and differentiation.
- TCDD's effects on gene expression share similarities with known tumor-promoting agents.