title: The role of ozone in tracheal cell transformation.
abstract: This project examined the potential role of ozone as a respiratory carcinogen by characterizing its ability to induce or modulate the preneoplastic transformation of rat tracheal epithelial cells. The chemical reactivity of ozone and the types of damage it can cause suggest that it may have a role in environmental carcinogenesis. Previous reports have described an increase in the incidence and number of lung tumors per animal in strain A mice exposed to ozone. However, the role of ozone in the development of the tumors has not been clear. Ozone also has been reported to act alone and synergistically with ionizing radiation to induce changes related to neoplasia in primary hamster embryo cells and in the mouse C3H/10T1/2 cell line in culture. Few other studies have examined the direct cytotoxic or transforming effects of ozone after in vivo or in vitro exposure of cells, and no studies have been reported on the comparative effects of ozone on respiratory cells exposed in vivo or in vitro. The induction of early preneoplastic changes in populations of rat tracheal epithelial cells by carcinogens can be detected and quantified in vitro after exposures in vivo or in vitro of tracheal epithelial cells. This cell culture and transformation system was used to characterize the transforming potency of ozone. Tracheal epithelial cells were isolated from Fischer-344/N rats that had been exposed for six hours per day, five days per week for one, two, or four weeks to 0, 0.12, 0.5, or 1.0 parts per million (ppm)* ozone (sea-level equivalents). Cell populations were examined in culture for increases in the frequency of preneoplastic variants. Rats exposed to ozone did not exhibit an increase in the frequency of preneoplastic tracheal cells, although exposed tracheas did exhibit dose-dependent morphological changes. Rat tracheal epithelial cells were given single, 40-minute in vitro exposures to concentrations of ozone that did not result in any detectable decrease in colony-forming efficiency (approximately 0.7 ppm) and to concentrations that resulted in approximately a 40% decrease (approximately 10 ppm). Exposed cultures were examined for increases in the frequency of preneoplastic variants. The results of these experiments, like those for the in vivo experiments described above, suggest that a single ozone exposure does not induce preneoplastic variants of rat tracheal epithelial cells. In contrast, cultures of rat tracheal cells exposed to 0.7 ppm ozone twice weekly for about five weeks exhibited approximately a twofold increase in the frequency of preneoplastic variants compared with control cultures.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Inhalation Toxicology Research Institute, Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87185.
authors.forename: D G
authors.initials: DG
authors.lastname: Thomassen
authors.forename: J R
authors.initials: JR
authors.lastname: Harkema
authors.forename: J D
authors.initials: JD
authors.lastname: Sun
authors.forename: N D
authors.initials: ND
authors.lastname: Stephens
authors.forename: W C
authors.initials: WC
authors.lastname: Griffith
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D002478:Cells, Cultured; D004347:Drug Interactions; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D010126:Ozone / Q000633:toxicity*; D011230:Precancerous Conditions / Q000139:chemically induced; D051381:Rats; D011916:Rats, Inbred F344; D013223:Statistics as Topic; D014132:Trachea / Q000166:cytology / Q000187:drug effects*
chemical_list: D002273:Carcinogens; D008769:Methylnitronitrosoguanidine; D010126:Ozone