Relative Potencies of Individual Polychlorinated Naphthalenes and Halowax Mixtures To Induce Ah Receptor-Mediated Responses
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文摘
Polychlorinated naphthalenes (PCNs) are ubiquitousenvironmental pollutants that are structurally similar toother polychlorinated diaromatic hydrocarbons (PCDHs),such as polychlorinated dibenzo-p-dioxins (PCDDs),dibenzofurans (PCDFs), and biphenyls (PCBs). Despitebeing ubiquitous, much less is known about the fate, transport,and biological effects of individual PCN congeners thanother PCDHs. The purpose of the current study was to utilizean in vitro assay (H4IIE-luc) to determine potenciesrelative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for20 individual PCNs (from 75 possible congeners) and 6 Halowaxmixtures. H4IIE rat hepatoma cells (H4IIE-Luc), whichare stably transfected with an Ah receptor (AhR)-controlledluciferase reporter gene construct, respond specificallyto AhR agonists and are thus a reasonable measure of AhR-mediated, or dioxin-like, activity. The most potentcongeners were 1,2,3,4,6,7-hexa-CN (PCN 66), 1,2,3,5,6,7-hexa-CN (PCN 67), and 1,2,3,4,5,6,7-hepta-CN (PCN 73), withrelative potencies as compared to TCDD of 0.004, 0.001,and 0.001, respectively. Significant structure-activityrelationships were observed. For example, lateral substitutionis an important determinant of AhR-mediated activity,but not sufficient, as illustrated by the inactivity of 2,3,6,7-tetra-CN to elicit AhR-mediated activity. Relative potenciesof the Halowax mixtures with AhR-mediated activity were0.0089, 0.000038, and 0.0000018 for 1051, 1014, and 1013,respectively. The relative potencies derived from this studywere applied to literature-derived data on concentrationsof PCN congeners in environmental mixtures to assessthe potential contribution of PCNs to total TCDD equivalents(TEQs) in environmentally weathered complex mixtures.

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