Activation of protein kinase B (PKB/Akt) and risk of lung cancer among rural women in India who cook with biomass fuel

Toxicol Appl Pharmacol. 2012 Feb 15;259(1):45-53. doi: 10.1016/j.taap.2011.12.002. Epub 2011 Dec 8.

Abstract

The impact of indoor air pollution (IAP) from biomass fuel burning on the risk of carcinogenesis in the airways has been investigated in 187 pre-menopausal women (median age 34years) from eastern India who cooked exclusively with biomass and 155 age-matched control women from same locality who cooked with cleaner fuel liquefied petroleum gas. Compared with control, Papanicolau-stained sputum samples showed 3-times higher prevalence of metaplasia and 7-times higher prevalence of dysplasia in airway epithelial cell (AEC) of biomass users. Immunocytochemistry showed up-regulation of phosphorylated Akt (p-Akt(ser473) and p-Akt(thr308)) proteins in AEC of biomass users, especially in metaplastic and dysplastic cells. Compared with LPG users, biomass-using women showed marked rise in reactive oxygen species (ROS) generation and depletion of antioxidant enzyme, superoxide dismutase (SOD) indicating oxidative stress. There were 2-5 times more particulate pollutants (PM(10) and PM(2.5)), 72% more nitrogen dioxide and 4-times more particulate-laden benzo(a)pyrene, but no change in sulfur dioxide in indoor air of biomass-using households, and high performance liquid chromatography estimated 6-fold rise in the concentration of benzene metabolite trans,trans-muconic acid (t,t-MA) in urine of biomass users. Metaplasia and dysplasia, p-Akt expression and ROS generation were positively associated with PM and t,t-MA levels. It appears that cumulative exposure to biomass smoke increases the risk of lung carcinogenesis via oxidative stress-mediated activation of Akt signal transduction pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Air Pollution, Indoor / adverse effects*
  • Air Pollution, Indoor / analysis
  • Antioxidants / metabolism
  • Biofuels*
  • Cooking
  • Enzyme Activation
  • Epithelial Cells / enzymology*
  • Epithelial Cells / pathology
  • Female
  • Humans
  • India
  • Inhalation Exposure / adverse effects
  • Inhalation Exposure / analysis
  • Logistic Models
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / epidemiology
  • Lung Neoplasms / etiology*
  • Lung Neoplasms / pathology
  • Particle Size
  • Particulate Matter / chemistry
  • Particulate Matter / toxicity
  • Particulate Matter / urine
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Reactive Oxygen Species / metabolism
  • Risk
  • Rural Population*
  • Signal Transduction
  • Socioeconomic Factors
  • Sputum / cytology
  • Surveys and Questionnaires

Substances

  • Antioxidants
  • Biofuels
  • Particulate Matter
  • Reactive Oxygen Species
  • Proto-Oncogene Proteins c-akt