PCB 9 exposure induces endothelial cell death while increasing intracellular calcium and ROS levels

Abstract

Cultured porcine endothelial cells were used to determine the effects of several congeners of polychlorinated biphenyls (PCBs) on cell viability and changes induced by these congeners on levels of intracellular calcium and reactive oxygen species (ROS). Cultured endothelial cells were prepared as a single suspension and run on flow cytometry. Cell viability, intracellular calcium, and ROS concentrations were simultaneously determined by using propidium iodide, Fluo-3, and dihydrorodamine, respectively. The congeners tested included two coplanar tetrachlorinated congeners that have no ortho chlorines, PCBs 77 and 80, a tri-chloro congener which does not have any ortho chlorine, PCB 39, a di-ortho, tetrachlorinated congener, PCB 52, and a mono-ortho congener, PCB 9. PCB 9 was cytotoxic at 5 μM within 5 min of exposure, and the toxicity increased with time and concentration. None of the other congeners showed consistent cytotoxicity. The cytotoxicity was roughly correlated with elevations in cellular ROS levels, but not with changes in intracellular calcium. To the best of our knowledge, toxicity of lower chlorinated, more volatile congeners such as PCB 9 has not been previously studied. These observations may be taken to explain the elevated risk of cardiovascular disease previously reported among residents living near to hazardous waste sites containing PCBs.

Trichloroethylene-mediated cytotoxicity in human epidermal keratinocytes is mediated by the rapid accumulation of intracellular calcium

“…12 Free Ca 2þ leads to the dissipation of mitochondrial membrane potential (MMP) and apoptosis. [13][14][15][16] ROS generation is one of the first and basic responses of the cells toward any kind of endogenous or environmental stress. 17 ROS production and degradation involve fine equilibrium, and during toxic insult, the equilibrium shifts toward massive ROS production.…”

“…12 Free Ca 2+ leads to the dissipation of mitochondrial membrane potential (MMP) and apoptosis. 13 – 16…”

Exposure to and health effects of volatile PCBs

“…They found that both congeners caused DNA damage as monitored by the comet assay, but that PCB 52 is significantly more potent. Both PCB 9 (2,5 dichlorobiphenyl) (28) and PCB 11 (29) generate reactive oxygen species, known to be a risk factor for cell damage and death. Ludewig et al (30) found that PCB 3 (4-monochlorobiphenyl) and/ or its metabolites increase mutations in rat liver.…”

Effects of Different Calorie Restriction Protocols on Oxidative Stress Parameters in a Transgenic Mouse Model of Breast Cancer

“…ROS levels are balanced at low to moderate concentrations by the antioxidant defense mechanisms under physiological conditions. However, cigarette smoking, toxicants, obesity, a highfat diet, and/or aging may lead to the disruption of this balance [9,10]. The severity of the consequences of this imbalance depends on a variety of factors, including the level and the location of ROS production, the efficacy of antioxidant systems, and the cellular targets of ROS [11].…”