The reduced apoptosis observed after particle e posure is not related to the pro inflammatory response and the EGF pathway. Moreover, water soluble as well as organic components such as heavy PAH, are able to mimic the effects triggered by PM2. 5, suggesting that such com pounds are involved in the antiapoptotic Enzalutamide pancreatic cancer effect. Finally, we identified the aryl hydrocarbon receptor as a molecu lar effector involved in the mechanism of the antiapopto tic effect of PM2. 5 on human bronchial epithelial cells. Results PM2. 5 are not cyctoto ic in human bronchial epithelial cells First, we were interested in finding out whether particles from Parisian ambient air have cytoto ic effect on human bronchial cells. Thus, we e posed 16HBE human bron chial epithelial cells to increasing amount of PM2.

5 AW from 1 to 50 ug cm2. Several hallmarks of apoptotic cell death recommended by the Nomenclature Committee on Cell Death were quantified by flow cytometry. Figure 1A shows that 24 h e posure to PM2. 5 AW induced none of several hallmarks of apoptosis such as ��m drop low staining o idative potential, phosphatidylserine e po sure and plasma membrane permeabilization. H2O2 is used here as positive con trol of apoptosis. Moreover, even when 16HBE cells were e posed for longer times to PM2. 5 AW, no significative increase of apoptotic parameters was observed suggesting that PM2. 5 AW do not have cytoto ic activity on human bronchial epithelial cells 16HBE e posed for 24 up to 72 hours.

In order to determine if this lack of to icity is specific to 16HBE cells, we e tended our study to other human bronchial epithelial cells, such as NCI H292 and BEAS 2B cell lines and to non differentiated primary human bronchial epithelial cells. Similarly to 16HBE cells, the dose effect study of PM2. 5 AW did not show any induction of apoptotic cell death, measured by ��m loss and PI high staining, with any of the three different cell types tested. Conversely, cells tested herein were not resistant to apoptosis induction as demonstrated after 24 h incubation with hydrogen pero ide. These results might be related to the batch of PM2. 5 used, in particular timing and location of particle collec tion. To test this hypothesis, we used several batches of Parisian PM2. 5 Auteuil Winter, Auteuil Summer, Vitry Winter or Vitry Summer collected in the Paris area Porte dAuteuil adjacent to a major highway and considered as a curbside station and a school playground at Vitry sur Seine in the suburb of Paris.

When bronchial cells were e posed 24 h to these PM2. 5, we noticed only an increased granular ity corresponding to particle uptake without any reduction in cell size. Apoptotic cell death was then quantified by ��m loss and plasma membrane permeabilization, and none of these parameters was significantly GSK-3 increased by e posure to the four different batches of PM2. 5.