Ozone remains one of the three most important air pollutants worldwide, yet little direct documented evidence of its genotoxicity exists. The interest in the pathology of ozone exposure and the molecular events that underlie its course stems from DNA damage caused by oxygen stress including hydroxyl radicals, superoxide, singlet oxygen, and hydrogen peroxide. Although the tissue damage associated with ozone inhalation occurs at both the conducting airway and the alveolus, the cellular and mechanistic processes underlying these events are less well understood. Ozone leads to the oxidative decomposition of polyunsaturated fatty acids. Ozone also depresses DNA replication in V79 Chinese hamster lung fibroblasts in a dose-dependent fashion (concentration, 1–10 ppm), which indicates that ozone or its reaction products may interact directly with DNA and inhibit replication. Ozone also linearizes circular DNA and induces ozone-sensitive mutant and pneumocytes to repair its DNA. DNA adducts have been implicated in aging, cellular transformation, mutagenesis, carcinogenesis, and cell death; DNA adducts are products of free radical damage. These events are all common in ozone exposure. Finally, DNA-binding proteins are potent positive and negative regulators, enhancers, or silencers of gene expression. Part of their action may be related to their ability to initiate the binding sequence of DNA transcription proteins and thus form complexes. Alteration of DNA-binding sites by ozone adducts may effect mRNA transcription due to altered binding by DNA-binding proteins. This altered transcription has been shown to effect growth factors involved in collagen and matrix regulation. The present review will address some of the complexities involved in ozone exposure. Evidence is presented indicating that DNA adducts can occur with ozone exposure and correlate adduct formation with pathobiology and/or DNA repair at various ozone levels.
ASJC Scopus subject areas
- Environmental Chemistry
- Environmental Science(all)
- Public Health, Environmental and Occupational Health
- Health, Toxicology and Mutagenesis