Particulate Matter (PM2.5) from Biomass Combustion Induces an Anti-Oxidative Response and Cancer Drug Resistance in Human Bronchial Epithelial BEAS-2B Cells.

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 (PM2.5) 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 PM2.5 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 PM2.5. Furthermore, cells exposed to PM2.5 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 PM2.5 induces molecular defense mechanisms, which prevent cellular damage and may thus explain the initially relative rare complications associated with PM2.5. 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.

Behavioral/lifestyle and immunologic factors associated with HPV infection among women older than 45 years.

BACKGROUND: Cervical human papilloma virus (HPV) detection increases after menopause, but its determinants need clarification. METHODS: In a case-control study nested within a 10,049 women cohort, we evaluated women 45 to 75 years old who acquired HPV infection and were HPV positive 5 to 6 years after enrollment (N = 252), and HPV-negative women as matched controls (N = 265). Detailed sexual behavior and cellular immune response were investigated. Odds ratios (OR) and attributable fractions were estimated. RESULTS: Women with 2+ lifetime partners had 1.7-fold (95% CI = 1.1-2.7) higher risk than monogamous women, with similar findings if their partners had other partners. Women with 2+ partners after last HPV-negative result had the highest risk (OR = 3.9; 95% CI = 1.2-12.4 compared with 0-1 partners). Weaker immune response to HPV-16 virus-like particles increased risk (OR = 1.7; 95% CI = 1.1-2.7 comparing lowest to highest tertile). Among women with no sexual activity in the period before HPV appearance, reduced immune response to phytohemagglutinin was the only determinant (OR = 2.9; 95% CI = 0.94-8.8). Twenty-one percent of infections were explained by recent sexual behavior, 21% by past sexual behavior, and 12% by reduced immune response. CONCLUSIONS: New infections among older women may result from sexual activity of women and/or their partners or reappearance of past (latent) infections possibly related to weakened immune response. IMPACT: HPV infections among older women are associated with current and past sexual exposures and possibly with immune senescence. The risk of cancer from these infections is likely to be low but could not be fully evaluated in the context of this study.