TOXIC HALOGENATED AROMATICS

描述：该项目建议进行几个相互关联的 对单独的多环芳烃(PAHs)和 重组的多环芳烃混合物以确定这些化合物的相互作用 化合物及其相互作用在多环芳烃诱导中的作用 致癌性。拟研究的多环芳烃化合物类别包括 多氯联苯、多氯二苯并对二恶英 (PCDDs)和多氯二苯并呋喃(PCDF)。建议数 研究内容包括：(1)细胞色素P4501A1的比较诱导分析 和重组的多环芳烃混合物和2-，3- 和&gt；4环多环芳烃组分，以确定其相对贡献 不同组份对混合物总诱导效力的影响； (2)将(1)扩展到包括其他由Ah受体介导的反应； (3)榄香烯选择性诱导细胞色素P1A2的研究 关于其毒理和致癌意义；及(4) 弱致癌物强致癌物相互作用的研究 微粒体P450酶诱导剂和弱致癌物 微粒体P450酶诱导物。所获得的结果将决定 多氯联苯与多氯二苯并二恶英/多氯二苯并呋喃之间非加成相互作用的程度以及 提供关键数据，可用于评估 HAHS风险评估的TEF模型。

Description: This project proposes to conduct several interrelated studies with individual polycyclic aromatic hydrocarbons (PAHs) and reconstituted PAH mixtures to determine the interactions of these compounds and the role of these interactions in PAH-induced carcinogenicity. The classes of PAH compounds to be studied include the polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs) and the polychlorinated dibenzofurans (PCDFs). The proposed studies include: (1) analysis of the comparative induction of CYP1A1 and CYP1A2 gene expression by a reconstituted PAH mixture and the 2-,3- and > 4-ring PAH fractions to determine the relative contributions of the different fractions to the overall induction potency of the mixture; (2) extension of (1) to include other Ah receptor-mediated responses; (3) investigation of the selective induction of CYP1A2 by acenaphthylene with regard to its toxicologic and carcinogenic significance; and (4) investigation of the interactions of strong carcinogens that are poor microsomal P450 enzyme inducers and weak carcinogens that are potent microsomal P450 enzyme inducers. The results obtained will determine the extent of the non-additive interactions between PCBs and PCDDs/PCDFs and provide critical data which can be used to evaluate the utility of the TEF model for risk assessment of HAHs.