Particulate matter selectively promotes macropinocytosis and malignant transformation-associated phenotypes in p53-impaired epithelial cells.

Abstract

Fine particulate matter (PM2.5; aerodynamic diameter <2.5µm) is associated with respiratory and cardiovascular disease and is classified, together with outdoor air pollution, as carcinogenic to humans. However, mechanisms underlying its tumor-promoting effects remain incompletely defined. We examined acute and repeated exposure to a European certified reference PM2.5 material in murine mammary epithelial and hamster respiratory cell models with intact or impaired p53 signaling. Stress and survival pathways, transcriptional responses, macropinocytosis, growth under nutrient limitation, cell-cycle effects, and anchorage-independent growth were assessed. PM2.5 activated oxidative-stress and cellular stress-response pathways across models. In contrast, p53-impaired cells exhibited distinct adaptive phenotypes, including enhanced macropinocytosis and increased growth under nutrient-limited conditions. Repeated PM2.5 exposure also increased anchorage-independent growth in a transformed mammary epithelial cell line. These findings indicate that chronic PM2.5 exposure may preferentially promote malignant phenotypes in cells with pre-existing defects in p53-dependent checkpoint control.