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
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.