title: Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location.
abstract: Particulate air pollution is widespread, yet we have little understanding of the long-term health implications associated with exposure. We investigated DNA damage, mutation, and methylation in gametes of male mice exposed to particulate air pollution in an industrial/urban environment. C57BL/CBA mice were exposed in situ to ambient air near two integrated steel mills and a major highway, alongside control mice breathing high-efficiency air particulate (HEPA) filtered ambient air. PCR analysis of an expanded simple tandem repeat (ESTR) locus revealed a 1.6-fold increase in sperm mutation frequency in mice exposed to ambient air for 10 wks, followed by a 6-wk break, compared with HEPA-filtered air, indicating that mutations were induced in spermatogonial stem cells. DNA collected after 3 or 10 wks of exposure did not exhibit increased mutation frequency. Bulky DNA adducts were below the detection threshold in testes samples, suggesting that DNA reactive chemicals do not reach the germ line and cause ESTR mutation. In contrast, DNA strand breaks were elevated at 3 and 10 wks, possibly resulting from oxidative stress arising from exposure to particles and associated airborne pollutants. Sperm DNA was hypermethylated in mice breathing ambient relative to HEPA-filtered air and this change persisted following removal from the environmental exposure. Increased germ-line DNA mutation frequencies may cause population-level changes in genetic composition and disease. Changes in methylation can have widespread repercussions for chromatin structure, gene expression and genome stability. Potential health effects warrant extensive further investigation.
authors.affiliation: Environmental and Occupational Toxicology Division, HECSB, Ottawa, ON, Canada K1A 0K9. carole_yauk@hc-sc.gc.ca
authors.forename: Carole
authors.initials: C
authors.lastname: Yauk
authors.forename: Aris
authors.initials: A
authors.lastname: Polyzos
authors.forename: Andrea
authors.initials: A
authors.lastname: Rowan-Carroll
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Somers
authors.forename: Roger W
authors.initials: RW
authors.lastname: Godschalk
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: Van Schooten
authors.forename: M Lynn
authors.initials: ML
authors.lastname: Berndt
authors.forename: Igor P
authors.initials: IP
authors.lastname: Pogribny
authors.forename: Igor
authors.initials: I
authors.lastname: Koturbash
authors.forename: Andrew
authors.initials: A
authors.lastname: Williams
authors.forename: George R
authors.initials: GR
authors.lastname: Douglas
authors.forename: Olga
authors.initials: O
authors.lastname: Kovalchuk
mesh_terms: D000393:Air Pollutants; D000397:Air Pollution; D000818:Animals; D018736:DNA Adducts; D004249:DNA Damage; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D018095:Germ-Line Mutation; D007221:Industry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D012091:Repetitive Sequences, Nucleic Acid; D013094:Spermatozoa / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D018736:DNA Adducts