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Toxicological Sciences 56, 303-312 (2000)
Copyright © 2000 by the Society of Toxicology

Morphological Transformation by 8-Hydroxy-2'-deoxyguanosine in Syrian Hamster Embryo (SHE) Cells

Haizhou Zhang, Yong Xu, Lisa M. Kamendulis and James E. Klaunig1

Division of Toxicology, Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46202

8-Hydroxy-2'-deoxyguanosine (OH8dG) is one of the most prevalent oxidative DNA modifications found in eukaryotic cells. Previous studies have suggested an association between OH8dG formation and carcinogenesis. However, it is unclear whether OH8dG formation results in the necessary genotoxic events for cancer development. In the present study, the formation of OH8dG and its ability to transform Syrian hamster embryo (SHE) cells was examined. Methylene blue, a photosensitizer that in the presence of light can generate singlet oxygen by a type II mechanism, was used to produce oxidative DNA damage (predominantly OH8dG) in SHE cells. Photoactivated methylene blue produced a dose-dependent increase in OH8dG as well as a dose-dependent increase in morphological transformation in SHE cells. SHE cells transfected with DNA that contained increasing concentrations of OH8dG displayed a dose-dependent increase in morphological transformation. Treatment with ß-carotene (a singlet oxygen quencher) inhibited both the formation of OH8dG and the induction of morphological transformation in photoactivated methylene blue–treated SHE cells. These results suggest that formation of OH8dG can induce morphological transformation and provide further support for a role of OH8dG formation in the carcinogenesis process.

Key Words: oxidative stress; OH8dG; SHE cell; morphological transformation; carcinogenicity; singlet oxygen.


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