Morphological transformation by 8-hydroxy-2 '-deoxyguanosine in Syrian hamster embryo (SHE) cells

Citation
Hz. Zhang et al., Morphological transformation by 8-hydroxy-2 '-deoxyguanosine in Syrian hamster embryo (SHE) cells, TOXICOL SCI, 56(2), 2000, pp. 303-312
Citations number
72
Categorie Soggetti
Pharmacology & Toxicology
Journal title
TOXICOLOGICAL SCIENCES
ISSN journal
10966080 → ACNP
Volume
56
Issue
2
Year of publication
2000
Pages
303 - 312
Database
ISI
SICI code
1096-6080(200008)56:2<303:MTB8'I>2.0.ZU;2-1
Abstract
8-Hydroxy-2'-deoxyguanosine (OH8dG) is one of the most prevalent oxidative DNA modifications found in eukaryotic cells. Previous studies have suggeste d 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 it s ability to transform Syrian hamster embryo (SHE) cells was examined. Meth ylene blue, a photosensitizer that in the presence of light can generate si nglet oxygen by a type II mechanism, was used to produce oxidative DNA dama ge (predominantly OH8dG) in SHE cells. Photoactivated methylene blue produc ed a dose-dependent increase in OH8dG as well as a dose-dependent increase in morphological transformation in SHE cells. SHE cells transfected with DN A that contained increasing concentrations of OH8dG displayed a dose-depend ent increase in morphological transformation. Treatment with beta-carotene (a singlet oxygen quencher) inhibited both the formation of OH8dG and the i nduction of morphological transformation in photoactivated methylene blue-t reated SHE cells. These results suggest that formation of OH8dG can induce morphological transformation and provide further support for a role of OH8d G formation in the carcinogenesis process.