title: Ozone inhalation leads to a dose-dependent increase of cytogenetic damage in human lymphocytes.
abstract: Ozone is an important constituent of ambient air pollution and represents a major public health concern. Oxidative injury due to ozone inhalation causes the generation of reactive oxygen species and can be genotoxic. To determine whether ozone exposure causes genetic damage in peripheral blood lymphocytes, we used a well-validated cytokinesis-block micronucleus Cytome assay. Frequencies of micronuclei (MN) and nucleoplasmic bridges (NB) were used as indicators of cytogenetic damage. Samples were obtained from 22 non-smoking healthy subjects immediately before and 24-hr after controlled 4-hr exposures to filtered air, 100 ppb, and 200 ppb ozone while exercising in a repeated-measure study design. Inhalation of ozone at different exposure levels was associated with a significant dose-dependent increase in MN frequency (P < 0.0001) and in the number of cells with more than one MN per cell (P <  .0005). Inhalation of ozone also caused an increase in the number of apoptotic cells (P = 0.002). Airway neutrophilia was associated with an increase in MN frequency (P = 0.033) independent of the direct effects of ozone exposure (P < 0.0001). We also observed significant increases in both MN and NB frequencies after exercise in filtered air, suggesting that physical activity is also an important inducer of oxidative stress. These results corroborate our previous findings that cytogenetic damage is associated with ozone exposure, and show that damage is dose-dependent. Further study of ozone-induced cytogenetic damage in airway epithelial cells could provide evidence for the role of oxidative injury in lung carcinogenesis, and help to address the potential public health implications of exposures to oxidant environments.
authors.affiliation: School of Public Health, University of California, Berkeley, California.
authors.forename: Nina
authors.initials: N
authors.lastname: Holland
authors.forename: Veronica
authors.initials: V
authors.lastname: Davé
authors.forename: Subha
authors.initials: S
authors.lastname: Venkat
authors.forename: Hofer
authors.initials: H
authors.lastname: Wong
authors.forename: Aneesh
authors.initials: A
authors.lastname: Donde
authors.forename: John R
authors.initials: JR
authors.lastname: Balmes
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Arjomandi
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000009:adverse effects / Q000032:analysis; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D015162:Micronucleus Tests; D009336:Necrosis; D009504:Neutrophils / Q000187:drug effects; D033281:Nontherapeutic Human Experimentation; D010126:Ozone / Q000008:administration & dosage* / Q000633:toxicity*
chemical_list: D010126:Ozone
keywords: air pollution; cytome assay; genotoxicity; oxidative stress; physical exercise