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.
| Frazer-Abel, Ashley A; McCue, Jesica M; Lazis, Sabine et al. (2007) Cigarette tar phenols impede T cell cycle progression by inhibiting cyclin-dependent kinases. Mol Immunol 44:488-93 |
| McCue, Jesica M; Lazis, Sabine; John Cohen, J et al. (2003) Hydroquinone and catechol interfere with T cell cycle entry and progression through the G1 phase. Mol Immunol 39:995-1001 |
