BIOASSAY FOR DIOXIN: WORK PLACE RELATED CUTANEOUS HAZARD

职业和环境暴露量2 3 7 8

Occupational and environmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) and its isomers and congeners at low concentrations induces chloracne and a wide spectrum of clinical pathologies in humans as well as teratogenesis, carcinogenesis and death in animals. This proposal is for the development of two in vitro systems, based on cell culture techniques using relevant biological markers, into routine assays for the detection and quantitation of very low levels of dioxin congeners and isomers. One system is the in vitro epithelial cell keratinization model of the in vivo hyperkeratinization response to dioxin exposure resulting in human chloracne. The second system is based on the development in this laboratory of a subline of epithelial cells which exhibit a marked increase in density dependent inhibition of replication and a change from a fusiform to "flat-cell" morphology upon exposure to very low concentration of 2,3,7,8 TCDD. Preliminary results from this laboratory on testing soot extracts from a dioxin and dibenzofuran contaminated building indicate that both these in vitro systems have the potential for development into rapid and inexpensive quantitative and qualitative assays for "dioxin-like" acnegenic potential in environmental and industrial samples. The goals of this proposal will be to 1) validate the specificity of these systems for dioxin congeners and isomers, improve the quantitative ability, and insure reliability of these two systems in order to establish them as routine assays, and 2) initiate preliminary studies to identify any ultrastructural changes of the cell organelles in relation to these dioxin induced effects and determine the feasibility of using these assays as a basis for further studies on the detection of dioxin-like acnegenic activity in serum samples. The latter will form the basis of future studies to allow routine monitoring of many high risk individuals for exposure to dioxin congeners and isomers as well as establishing a data base for use in determining the significance of specific blood levels of these compounds in regard to subsequent clinical manisfestations.