title: A common carcinogen benzo[a]pyrene causes neuronal death in mouse via microglial activation.
abstract: BACKGROUND
  Benzo[a]pyrene (B[a]P) belongs to a class of polycyclic aromatic hydrocarbons that serve as micropollutants in the environment. B[a]P has been reported as a probable carcinogen in humans. Exposure to B[a]P can take place by ingestion of contaminated (especially grilled, roasted or smoked) food or water, or inhalation of polluted air. There are reports available that also suggests neurotoxicity as a result of B[a]P exposure, but the exact mechanism of action is unknown.
  
  
  RESULTS
  Using neuroblastoma cell line and primary cortical neuron culture, we demonstrated that B[a]P has no direct neurotoxic effect. We utilized both in vivo and in vitro systems to demonstrate that B[a]P causes microglial activation. Using microglial cell line and primary microglial culture, we showed for the first time that B[a]P administration results in elevation of reactive oxygen species within the microglia thereby causing depression of antioxidant protein levels; enhanced expression of inducible nitric oxide synthase, that results in increased production of NO from the cells. Synthesis and secretion of proinflammatory cytokines were also elevated within the microglia, possibly via the p38MAP kinase pathway. All these factors contributed to bystander death of neurons, in vitro. When administered to animals, B[a]P was found to cause microglial activation and astrogliosis in the brain with subsequent increase in proinflammatory cytokine levels.
  
  
  CONCLUSIONS
  Contrary to earlier published reports we found that B[a]P has no direct neurotoxic activity. However, it kills neurons in a bystander mechanism by activating the immune cells of the brain viz the microglia. For the first time, we have provided conclusive evidence regarding the mechanism by which the micropollutant B[a]P may actually cause damage to the central nervous system. In today's perspective, where rising pollution levels globally are a matter of grave concern, our study throws light on other health hazards that such pollutants may exert.
authors.affiliation: National Brain Research Centre, Manesar, Haryana, India.
authors.forename: Kallol
authors.initials: K
authors.lastname: Dutta
authors.forename: Debapriya
authors.initials: D
authors.lastname: Ghosh
authors.forename: Arshed
authors.initials: A
authors.lastname: Nazmi
authors.forename: Kanhaiya Lal
authors.initials: KL
authors.lastname: Kumawat
authors.forename: Anirban
authors.initials: A
authors.lastname: Basu
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology* / Q000633:toxicity; D002273:Carcinogens / Q000494:pharmacology* / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004785:Environmental Pollutants / Q000494:pharmacology / Q000633:toxicity; D018836:Inflammation Mediators; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D009569:Nitric Oxide / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D002273:Carcinogens; D016207:Cytokines; D004785:Environmental Pollutants; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D001564:Benzo(a)pyrene