Higher AgNOR Expression in Metaplastic and Dysplastic Airway Epithelial Cells Predicts the Risk of Developing Lung Cancer in Women Chronically Exposed to Biomass Smoke

J Environ Pathol Toxicol Oncol. 2015;34(1):35-51. doi: 10.1615/jenvironpatholtoxicoloncol.2015010708.


We evaluated AgNOR expression in airway epithelial cells (AECs) as a risk factor of lung carcinogenesis in 228 nonsmoking women exposed to biomass fuel (BMF). A total of 185 age-matched women who cooked with cleaner fuel (liquefied petroleum gas [LPG]) were enrolled as study controls. Compared with controls, Papanicolaou-stained sputum samples showed 4 and 8 times higher prevalence of metaplasia and dysplasia, respectively, in AECs of BMF users. AgNOR staining showed significantly larger numbers of dots and larger size and percentage of AgNOR-occupied nuclear area in normal AECs of BMF users than in controls. Interestingly, AgNOR parameters increased dramatically when the cells were transformed from normalcy to metaplasia and dysplasia. Compared with LPG users, BMF users showed a marked rise in reactive oxygen species (ROS) generation and a depletion of superoxide dismutase (SOD), indicating oxidative stress. Indoor air of BMF-using households had 2-5 times more particulate pollutants (PM10 and PM2.5), 73% more nitrogen dioxide (NO2), and 4 times more particulate-laden benzo(a)pyrene [B(a)P], but no difference in sulfur dioxide was observed. A high-performance liquid chromatography (HPLC) study estimated a 6-fold rise in benzene metabolite trans, trans-muconic acid (t,t-MA) in urine of BMF users. After controlling confounding factors using multivariate logistic regression, positive associations were observed between cellular changes, AgNOR parameters, and PM10, PM2.5, NO2, B(a)P, and t,t-MA levels, especially the concentration of B(a)P. In conclusion, cumulative exposure to biomass smoke causes oxidative stress and enhances AgNOR expression in precancerous metaplastic and dysplastic AECs and appears to be a risk factor for developing lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Air Pollution, Indoor / adverse effects*
  • Antigens, Nuclear / analysis*
  • Biomass
  • Bronchi / chemistry
  • Bronchi / pathology*
  • Epithelial Cells / pathology
  • Female
  • Humans
  • Logistic Models
  • Lung Neoplasms / etiology*
  • Metaplasia
  • Oxidative Stress
  • Particulate Matter / analysis
  • Precancerous Conditions / complications*
  • Reactive Oxygen Species / metabolism
  • Risk
  • Smoke / adverse effects*
  • Superoxide Dismutase / metabolism


  • Antigens, Nuclear
  • Particulate Matter
  • Reactive Oxygen Species
  • Smoke
  • nucleolar organizer region associated proteins
  • Superoxide Dismutase