Cell Cycle Disruption by Hydroquinone and Catechol

产品说明：（改编自申请人摘要）：在环境免疫毒物中，苯及其衍生物的产生量最大，人体接触最广，特别是由于吸烟。其中，氢化奎宁（HQ）和儿茶酚是体外几种T细胞反应的有效抑制剂。本研究的长期目标是通过阐明暴露于这些苯衍生物影响人淋巴细胞功能的机制来确定HQ和儿茶酚如何抑制细胞免疫。本研究中要检验的假设是HQ和儿茶酚通过干扰细胞周期进程的正常顺序来破坏T细胞应答。为了确定这些酚类化合物的分子作用机制，将使用正常的人淋巴细胞进行以下具体目标：检查HQ和儿茶酚诱导的细胞周期阻滞的动力学和剂量范围。通过评估调节T细胞周期进入（或G 0退出）的事件，确定体外急性暴露于HQ和儿茶酚对IL-2非依赖性感受态诱导的影响。评价体外急性暴露于HQ和儿茶酚对调节IL-2依赖性G1期进展和细胞存活的事件的影响。

DESCRIPTION: (Adapted from the Applicant's Abstract): Among the environmental immunotoxicants, benzene and its derivatives are produced in the greatest quantities have the widest human exposure, particularly as a result of cigarette smoking. Of these, hydroquinine (HQ) and catechol are potent inhibitors of several T cell responses in vitro. The long term objective of this research is to determine how HQ and catechol suppress cellular immunity by elucidating mechanisms by which exposure to these benzene derivatives affect human lymphocyte function. The hypothesis to be tested in this study is that HQ and catechol disrupt T cell responses by interfering with the normal sequence of cell cycle progression. In order to determine the molecular mechanisms of action of these phenolic compounds, the following specific aims will be undertaken using normal, human lymphocytes: Examine the kinetics and dose range of HQ- and catechol-induced cell cycle block. Determine the effects of acute exposure in vitro to HQ and catechol on IL-2 independent induction of competence by evaluating events that regulate T cell cycle entry (or G0 exit). Evaluate the effects of acute exposure in vitro to HQ and catechol on events that regulate IL-2 dependent G1 phase progression and cell survival.