Comparison Of The Effects Of Cisplatin And A Novel Platinum Polymer Conjugate On The Production Of Reactive Oxygen Species By Human Neutrophils In Vitro

We have investigated the effects of cisplatin and 2 novel, water-soluble platinum (Pt) polymer conjugates, Pt-6 and Pt-7, on the production of reactive oxygen species (ROS) by unstimulated human neutrophils, as well as by cells activated with phorbol myristate acetate (PMA). Production of ROS was measured using a lucigenin-enhanced chemiluminescence (LECL) procedure. Addition of cisplatin to neutrophils resulted in an abrupt, dose-related, but small increase in the spontaneous generation of ROS by the cells, whereas the PMA-activated responses were substantially increased by pretreatment of neutrophils with the antineoplastic agent. Importantly, neither the spontaneous nor the PMA-activated LECL responses of neutrophils were altered after treatment with either Pt-6 or Pt-7. Taken together with their impressive and selective anti-proliferative effects on tumor cells, the absence of pro-oxidative interactions of Pt-6 and Pt-7 with human neutrophils further underscores the clinical potential of these novel anticancer agents.