Cell Cycle Disruption by Hydroquinone and Catechol

描述：(改编自申请人的摘要)：在环境免疫毒物中，苯及其衍生物的产量最大，对人体的接触范围最广，特别是由于吸烟。其中，氢奎宁(HQ)和儿茶酚在体外是几种T细胞反应的有效抑制剂。这项研究的长期目标是通过阐明接触这些苯衍生物影响人类淋巴细胞功能的机制来确定HQ和儿茶酚是如何抑制细胞免疫的。这项研究要检验的假设是，HQ和儿茶酚通过干扰细胞周期进程的正常顺序来扰乱T细胞的反应。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特定目标：检测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G0退出)的事件，确定在体外急性暴露于HQ和儿茶酚对IL-2非依赖性能力诱导的影响。评估体外急性暴露于HQ和儿茶酚对调节IL-2依赖的G1期进程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.