title: Mustard gas exposure and carcinogenesis of lung.
abstract: Sulfur mustard (SM), also known as mustard gas, is an alkylating compound used as a chemical weapon in World War I and by Iraqi forces against Iranians and indigenous Iraqi Kurds during the Iran-Iraq War of the 1980s. Although SM is a proven carcinogen there are conflicting views regarding the carcinogenicity of a single exposure. The present study characterizes lung cancers formed in mustard gas victims from the Iran-Iraq War.
  
  
  METHODS
  Demographic information and tumor specimens were collected from 20 Iranian male lung cancer patients with single high-dose SM exposures during the Iran-Iraq War. Formalin-fixed, paraffin-embedded lung cancers were analyzed by immunohistochemistry for p53 protein. In addition, DNA was extracted from the tissues, PCR amplified and sequenced to identify mutations in the p53 and KRAS genes associated with SM exposure.
  
  
  RESULTS
  A relatively early age of lung cancer onset (ranging from 28 to 73 with a mean of 48) in mustard gas victims, particularly those in the non-smoking population (mean age of 40.7), may be an indication of a unique etiology for these cancers. Seven of the 20 patients developed lung cancer before the age of 40. Five of 16 cancers from which DNA sequence data was obtainable provided information on eight p53 mutations (within exons 5-8). These mutations were predominately G to A transitions; a mutation consistent with the DNA lesion caused by SM. Two of the lung cancers had multiple p53 point mutations, similar to results obtained from factory workers chronically exposed to mustard agent. No mutations were detected in the KRAS gene.
  
  
  CONCLUSIONS
  The distinguishing characteristics of lung carcinogenesis in these mustard gas victims suggest that a single exposure may increase the risk of lung cancer development in some individuals.
authors: Department of Molecular and Cell Biology, University of Connecticut, USA. alireza_hosseini50@yahoo.com
authors: Alireza
authors: A
authors: Hosseini-khalili
authors: David D
authors: DD
authors: Haines
authors: Ehsan
authors: E
authors: Modirian
authors: Mohammadreza
authors: M
authors: Soroush
authors: Shahriar
authors: S
authors: Khateri
authors: Rashmi
authors: R
authors: Joshi
authors: Kazem
authors: K
authors: Zendehdel
authors: Mostafa
authors: M
authors: Ghanei
authors: Charles
authors: C
authors: Giardina
mesh_terms: D000328:Adult; D000368:Aged; D002619:Chemical Warfare Agents / Q000633:toxicity*; D016158:Genes, p53; D006801:Humans; D019570:Inhalation Exposure; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009151:Mustard Gas / Q000633:toxicity*; D009154:Mutation
chemical_list: D002619:Chemical Warfare Agents; D009151:Mustard Gas