Quantitative Analysis of Constitutive and 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced Cytochrome P450 1B1 Expression in Human Lymphocytes

作者: Karah M. Lanier , Jean A. Grassman , Scott A. Masten , Nigel J. Walker , Diane L. Spencer

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摘要: Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) results in a broad spectrum of biological responses, including altered metabolism, disruption normal hormone signaling pathways, reproductive and developmental effects, cancer. Cytochrome P450 1B1 (CYP1B1) is dioxin-inducible gene that active the formation 4-hydroxyestradiol, potentially genotoxic catechol estrogen. Therefore, analysis CYP1B1 humans may be useful establishing relationships between dioxin exposure adverse health effects. In this study, we examined expression human peripheral blood lymphocytes unexposed individuals using quantitative reverse transcription-PCR method. Absolute RNA levels varied more than 30-fold uncultured mononuclear cells obtained from 10 individuals. vitro treatment mitogen-stimulated with TCDD for 1-5 days culture resulted peak induction after 3 days. The was dose-dependent, exhibited maximum response above nM TCDD, greatly among different However, half maximal dose required similar comparable observed MCF-7 HepG2 cell lines. These observations indicate exhibits variable constitutive inducible by magnitude varies within population. data define suitability use as mechanistically based biomarker ongoing molecular epidemiological studies populations exposed dioxins related chemicals bind aromatic hydrocarbon receptor.

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