title: Lack of genotoxicity of bitumen fumes in transgenic mouse lung.
abstract: During hot application of bitumen containing materials, e.g. in hot paving or roofing, fumes are emitted that contain polycyclic aromatic compounds. Previous studies with rodents exposed to bitumen and coal-tar fume condensates showed formation of DNA adducts. In order to clarify the genotoxicity of bitumen fumes, we designed a study by using mice carrying a reporter gene for mutagenesis analysis and exposed by nose-only to a constant and reproducible aerosol of bitumen fumes. We analyzed the genotoxic activity of inhaled bitumen fumes generated under those controlled conditions through the induction of mutation and DNA adducts in Big Blue mice. Mice were exposed to bitumen fumes (100 mg/m(3) total particulate matter) 6 h per day during 5 days by nose-only in an inhalation chamber designed in our laboratory. Following a 30-day fixation period, the experiment was terminated and lung DNA was extracted for mutant frequency and adduct determinations. The mutant frequency was determined using the cII and the lacI mutant analysis systems. In, addition, 61 and 54 mutants were sequenced in control and exposed groups, respectively. The study did not show any mutation or adduct induction in the exposed group compared to the control group: cII mutant frequencies were 11.0+/-4.5x10(-5) and 11.0+/-4.8x10(-5) in control and exposed lungs, respectively. Identically, using the lacI mutation detection system, the mutant frequencies were 6.4+/-3.1x10(-5) and 5.8+/-2.0x10(-5). The mutation spectra of both series were quite similar with regard to transition and transversion frequencies. The absence of genotoxicity in the group exposed to 100 mg/m(3) bitumen is discussed with regard to dosage of inhaled polycyclic aromatic compounds and species.
authors.affiliation: Département Polluants et Santé, Institut National de Recherche et de Sécurité, Avenue de Bourgogne, 54501, Cedex, Vandoeuvre, France.
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Micillino
authors.forename: Catherine
authors.initials: C
authors.lastname: Coulais
authors.forename: Stéphane
authors.initials: S
authors.lastname: Binet
authors.forename: Marie Claire
authors.initials: MC
authors.lastname: Bottin
authors.forename: Gérard
authors.initials: G
authors.lastname: Keith
authors.forename: David
authors.initials: D
authors.lastname: Moulin
authors.forename: Bertrand Henri
authors.initials: BH
authors.lastname: Rihn
mesh_terms: D000336:Aerosols; D000818:Animals; D002855:Chromatography, Thin Layer; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D018736:DNA Adducts / Q000187:drug effects; D005740:Gases / Q000633:toxicity*; D017930:Genes, Reporter / Q000235:genetics; D006838:Hydrocarbons / Q000633:toxicity*; D007763:Lac Operon / Q000235:genetics; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation / Q000187:drug effects
chemical_list: D000336:Aerosols; D018736:DNA Adducts; D005740:Gases; D006838:Hydrocarbons; D009153:Mutagens; C006647:asphalt; D004247:DNA