title: Mutation spectra of smoky coal combustion emissions in Salmonella reflect the TP53 and KRAS mutations in lung tumors from smoky coal-exposed individuals.
abstract: Nonsmoking women in Xuan Wei County, Yunnan Province, China who use smoky coal for cooking and heating in poorly ventilated homes have the highest lung cancer mortality rate in China, and their lung cancer is linked epidemiologically to their use of smoky coal. The emissions contain 81% organic matter, of which 43% is polycyclic aromatic hydrocarbons (PAHs). Exposure assessment and molecular analysis of the lung tumors from nonsmoking women who use smoky coal strongly indicate that PAHs in the emissions are a primary cause of the elevated lung cancer in this population. Here we have determined the mutation spectra of an extract of smoky coal emissions in Salmonella TA98 and TA100; the extract was not mutagenic in TA104. The extract was 8.7 x more mutagenic in TA100 with S9 than without (8.7 rev/microg versus 1.0 rev/microg) and was >3 x more mutagenic in TA100 than in TA98--consistent with a prominent role for PAHs in the mutagenicity of the extract because PAHs are generally more mutagenic in the base-substitution strain TA100 than in the frameshift strain TA98. The extract induced only a hotspot mutation in TA98; another combustion emission, cigarette smoke condensate (CSC), also induces this single class of mutation. In TA100, the mutation spectra of the extract were not significantly different in the presence or absence of S9 and were primarily (78-86%) GC --> TA transversions. This mutation is induced to a similar extent by CSC (78%) and the PAH benzo[a]pyrene (B[a]P) (77%). The frequency of GC --> TA transversions induced in Salmonella by the extract (78-86%) is similar to the frequency of this mutation in the TP53 (76%) and KRAS (86%) genes of lung tumors from nonsmoking women exposed to smoky coal emissions. The mutation spectra of the extract reflect the presence of PAHs in the mixture and support a role for PAHs in the induction of the mutations and tumors due to exposure to smoky coal emissions.
authors.affiliation: Department of Environmental Science and Engineering, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Granville
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Hanley
authors.forename: Judy L
authors.initials: JL
authors.lastname: Mumford
authors.forename: David M
authors.initials: DM
authors.lastname: DeMarini
mesh_terms: D002681:China; D003031:Coal / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D005260:Female; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics*; D009152:Mutagenicity Tests / Q000379:methods; D009154:Mutation; D012475:Salmonella / Q000187:drug effects / Q000235:genetics*; D012906:Smoke / Q000009:adverse effects*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D003031:Coal; D012906:Smoke; D016159:Tumor Suppressor Protein p53