Loertscher, J. A., C.A.R. Ivarie, M.A. Weitzel, and B. L. Allen-Hoffmann. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) Causes Alterations in Differentiation of Keratinocytes in Organotypic Culture. The Toxicologist 1999. 48(1S): 76. Abstract # 356.

2,3,7,8 - tetrachlorodibenzo-p-dioxin - 01746-01-6;

Human exposure to the environmental toxin TCDD produces a severe skin pathology known as chloracne. Although several laboratories have previously reported on the aryl hydrocarbon receptor (AhR)-mediated cellular responses of normal human or rodent keratinocytes to TCDD in vitro, little evidence has been available to link these observations to the specific pathology observed in skin. To approximate the three dimensional microenvironment of human skin, we have established organotypic cultures utilizing BD-1-Ep/SL cells, a novel human keratinocyte cell line. The BD-1-Ep/SL cell line was isolated in our laboratory and is identical to normal keratinocytes in its growth and differentiation characteristics. These cells differentiate normally in vitro and are morphologically indistinguishable from normal human keratinocytes at both the light and electron microscope level. The BC-1-Ep/SL keratinocytes are immortal and have been shown to be non-tumorigenic in nu/nu mice. Upon treatment of the organotypic model system with TCDD, we have observed al altered morphology as compared to controls. In treated samples we observed a thickening of the granular and cornified superbasal layers of keratinocytes in organotypic culture. This phenomenon was observed in organotypic culture seeded with normal human keratinocytes and subsequently with BD-1-Ep/SL keratinocytes. We present new data on the differentiation characteristics of TCDD-treated kertatinocyte in organotypic culture and examine the effect of TCDD on epithelial-mesenchymal interactions in vitro.