Particulate Matter (PM_2.5) from Biomass Combustion Induces an Anti-Oxidative Response and Cancer Drug Resistance in...

Nearly half of the world's population relies on combustion of solid biofuels to cover fundamental energy demands. Epidemiologic data demonstrate that particularly long-term emissions adversely affect human health. However, pathological molecular mechanisms are insufficiently characterized. Here we demonstrate that long-term exposure to fine particulate matter (PM_2.5) from biomass combustion had no impact on cellular viability and proliferation but increased intracellular reactive oxygen species (ROS) levels in bronchial epithelial BEAS-2B cells. Exposure to PM_2.5 induced the nuclear factor erythroid 2-related factor 2 (Nrf2) and mediated an anti-oxidative response, including enhanced levels of intracellular glutathione (GSH) and nuclear accumulation of heme oxygenase-1 (HO-1). Activation of Nrf2 was promoted by the c-Jun N-terminal kinase JNK1/2, but not p38 or Akt, which were also induced by PM_2.5. Furthermore, cells exposed to PM_2.5 acquired chemoresistance to doxorubicin, which was associated with inhibition of apoptosis and elevated levels of GSH in these cells. Our findings propose that exposure to PM_2.5 induces molecular defense mechanisms, which prevent cellular damage and may thus explain the initially relative rare complications associated with PM_2.5. However, consistent induction of pro-survival pathways may also promote the progression of diseases. Environmental conditions inducing anti-oxidative responses may have the potential to promote a chemoresistant cellular phenotype.