TOXIC HALOGENATED AROMATICS

说明：本项目拟开展几项相互关联的 对单个多环芳烃的研究， 重组PAH混合物，以确定这些相互作用 化合物以及这些相互作用在PAH诱导的 致癌性研究的多环芳烃化合物类别包括 多氯联苯（PCBs）、多氯二苯并对二恶英 多氯二苯并呋喃（PCDFs）。拟议 研究内容包括：（1）比较分析CYP 1A 1的诱导作用 和CYP 1A 2基因表达的重组PAH混合物和2-，3- 和> 4-环PAH组分，以确定 不同组分对混合物的总诱导效力的影响; (2)（1）的扩展以包括其它Ah受体介导的应答; (3)苊烯对细胞色素P4501 A2选择性诱导作用的研究 关于其毒理学和致癌意义;和（4） 研究强致癌物与弱致癌物之间的相互作用 微粒体P450酶诱导剂和强效弱致癌物 微粒体P450酶诱导剂。所获得的结果将决定 多氯联苯与多氯二苯并对二恶英/多氯二苯并呋喃之间的非加和性相互作用的程度， 提供关键数据，可用于评估 危险性评价的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.