ABSTRACT
This chapter discusses the scenarios of simultaneous tumor growth inhibition and tumor promotion resulting from tetrachlorodibenzo-p-dioxin (TCDD) exposure, while seemingly contradictory, are likely attributable to the cell- and tissue-specific effects of dioxin. It provides the experiments that demonstrate the diversity among microarrays and the challenges associated with examining the effects of TCDD, a clear example of the complexity of global gene expression patterns associated with dioxin exposure. In some cases, human body burdens of dioxin range from 13 to 7000 ng/kg, a range that is associated with developmental toxicity in laboratory animals exposed in utero. Functional assays of cell proliferation, toxicity, and apoptosis serve to complement gene expression analyses by connecting altered genes that at first appear to have unrelated or contradictory functions. The chapter utilizes the available gene knockout and transgenic mice to their full potential to elucidate molecular targets of TCDD in the presence, as well the absence, of aryl hydrocarbon receptor, CYP1A1, CYP1A2, and CYP1B1.
