Specific induction of oxidative stress in terminal bronchiolar Clara cells during dimethylarsenic-induced lung tumor promoting process in mice

• Published in: Cancer letters Vol. 230; no. 1; pp. 57 - 64
• Main Authors: An, Yan, Kato, Koichi, Nakano, Masayuki, Otsu, Hiroshi, Okada, Shoji, Yamanaka, Kenzo
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 08.12.2005; Elsevier Limited
• Subjects: 4-Hydroxy-2-nonenal; Animals; Arsenic; Cacodylic Acid - toxicity; Cell Transformation, Neoplastic - drug effects; Clara cell; Deoxyribonucleic acid; Dimethylarsinic acid; DNA; Drinking water; Free radicals; Glycerol; Herbicides - toxicity; Lipid Peroxidation; Lung - cytology; Lung Neoplasms - chemically induced; Lung Neoplasms - physiopathology; Lung tumor promotion; Male; Mice; Microscopy; Microscopy, Electron, Transmission; Oxidative Stress; Rodents; Trivalent dimethylated arsenic; Tumorigenesis; Tumors; Japan; 4-Hydroxy-2-nonenal; Oxidative stress; Trivalent dimethylated arsenic; Clara cell; Dimethylarsinic acid; Lung tumor promotion
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2004.12.029

The induction of oxidative stress in pulmonary cells during the process of lung tumor promotion by dimethylarsinic acid (DMA), a main metabolite of inorganic arsenics in mammals, was examined by immunohistochemical analysis using a specific antibody against 4-hydroxy-2-nonenal (4HNE) adducts, which are major aldehydic metabolites of lipid peroxidation. We demonstrated that 4HNE-modified proteins existed specifically in the secretory granules in terminal bronchiolar Clara cells. Furthermore, the degree of positive staining increased with the duration of DMA administration. Transmission electron microscopy revealed morphological changes in the Clara cells of DMA-treated mice. These results suggest that Clara cells are the major target cell for DMA-induced oxidative stress and that the cells may play an important role in the lung tumor promotion process in mice.