title: Mutagenic fingerprint of ozone in human cells.
abstract: Ozone is an important factor in urban pollution and represents a major concern for human health. The chemical reactivity of ozone toward biological targets and particularly its genotoxicity supports a possible link between exposure and cancer risk, but no molecular data exist on its mutagenic potential in human cells. Using a shuttle vector, we showed that ozone is indeed a potent mutagen and we characterized the mutation spectrum it produced in human cells. Almost all mutations are base substitutions, essentially located at G:Cs (75%), typical of reactive oxygen species (ROS), but occurring in a specific pattern, i.e. a similar extent of GC:TA (28%), GC:CG (23%) and GC:AT (23%). The targeted distribution of mutations and identification of hotspot sequences define the first molecular fingerprint of mutations induced by ozone in human cells. Possible applications derived from our results with respect to ozone genotoxicity should help determining quantifiable biomarkers of ozone exposure in human health, especially for carcinogenesis.
authors.affiliation: Laboratory of Genetic Instability and Cancer, UPR 2169 CNRS, Institute of Cancer Research, 7 rue Guy Moquet, B.P.8, 94801 Villejuif, Cedex, France.
authors.forename: Soraia A C
authors.initials: SA
authors.lastname: Jorge
authors.forename: Carlos F M
authors.initials: CF
authors.lastname: Menck
authors.forename: Helmut
authors.initials: H
authors.lastname: Sies
authors.forename: Martin R
authors.initials: MR
authors.lastname: Osborne
authors.forename: David H
authors.initials: DH
authors.lastname: Phillips
authors.forename: Alain
authors.initials: A
authors.lastname: Sarasin
authors.forename: Anne
authors.initials: A
authors.lastname: Stary
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D020856:AT Rich Sequence / Q000187:drug effects; D001483:Base Sequence; D002461:Cell Line, Transformed; D002478:Cells, Cultured / Q000187:drug effects / Q000502:physiology*; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects*; D020862:GC Rich Sequence / Q000187:drug effects*; D005822:Genetic Vectors; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D007763:Lac Operon / Q000187:drug effects* / Q000235:genetics*; D008969:Molecular Sequence Data; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects; D010083:Oxidants, Photochemical / Q000633:toxicity*; D010126:Ozone / Q000633:toxicity*
chemical_list: D010083:Oxidants, Photochemical; D006147:Guanine; D010126:Ozone; C078307:8-oxo-7,8-dihydrodeoxyguanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA