Molecular basis of dioxin actions: Evidence supporting chemoprotection

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin). a highly publicized e nvironmental contaminant, was shown to be chemoprotective against breast ca ncer in both rats and mice in bioassays conducted in the late 1970s. This f inding went largely unnoticed as investigators focused on animal tumors tha t were increased by dioxin. The position that dioxin causes human tumors re mains a subject for debate; however. recent epidemiological studies of a po pulation highly exposed to dioxin in 1976 as a result of an industrial acci dent suggest that women with higher dioxin body burdens may have a lower in cidence of breast cancer. With the growth of new knowledge about the molecu lar basis of dioxin actions in humans and animals, it is clear that most of the responses produced by this agent are initiated by a specific recogniti on protein (designated the Ah receptor) found in almost all animal and huma n tissues and organs. The recognition event between the Ah receptor and env ironmental agents like dioxin is due to the formation of a complex. We have observed that in the presence of dioxin. the Ah receptor turns off prolife ration in tumor cells and suppresses the ability of these cells to invade n ormal tissue. We believe that these findings provide a molecular and bioche mical basis for understanding the chemoprotective mechanisms suggested by t he findings of rodent bioassays and could lead to the development of novel therapeutic agents targeting the Ah receptor.