TCDD, Dioxin

TCDD is the prototype for a class of halogenated aromatic hydrocarbons, which appear to have a common mechanism of action and to produce similar effects, although they differ in potency. TCDD achieved notoriety in the 1970's when it was discovered to be a contaminant in the herbicide Agent Orange and was shown to produce birth defects in rodents. It continues to generate concern because of its widespread distribution as an environmental contaminant, its persistence within the food chain, and its toxic potency.

TCDD can produce both adaptive (beneficial) and adverse effects. One adaptive response is the induction of xenobiotic-metabolizing enzymes, which catalyze the metabolic processing of lipophilic chemicals to water-soluble derivatives, thereby facilitating their elimination via the urine. We are analyzing one such adaptive response, the induction of CYP1A1 gene transcription in mouse hepatoma cells, as a model for understanding the mechanism of dioxin action.

In experimental animals, TCDD elicits numerous adverse effects, raising concern about the risk it poses to public health. In humans, TCDD can produce the skin condition known as chloracne; the possibility that it also produces cancer, endocrine alterations, immunological changes, and/or birth defects (as it does in animals) is the subject of debate. Many individuals have been exposed to TCDD, primarily from dietary sources, although occupational and accidental exposures have also occurred. Thus, the population at potential risk for adverse effects is large. TCDD is a poor substrate for detoxification enzymes; therefore, it tends to persist in the body. raising the concern that repeated exposures, even to "low" concentrations, may evoke harmful health effects. Knowledge of the mechanism of dioxin action may help in accessing its health risks while generating new insights into the regulation of mammalian gene expression.

 

 


Dept. of Molecular Pharmacology

Stanford University Medical Center

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Originally created by Felix W. Frueh
Updated and maintained by Caroline Johnston
Updated 7/99