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

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 ev...

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Veröffentlicht in:Toxicological sciences 2000-08, Vol.56 (2), p.303-312
Hauptverfasser: HAIZHOU ZHANG, YONG XU, KAMENDULIS, L. M, KLAUNIG, J. E
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YONG XU
KAMENDULIS, L. M
KLAUNIG, J. E
description 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 beta-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.
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subjects 8-hydroxy-2'-deoxyguanosine
Animals
beta Carotene - pharmacology
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Cell Transformation, Neoplastic - chemically induced
Cricetinae
Deoxyguanosine - analogs & derivatives
Deoxyguanosine - toxicity
Dose-Response Relationship, Drug
Embryo, Mammalian - drug effects
Embryo, Mammalian - pathology
Foods and miscellaneous
Free Radical Scavengers - pharmacology
Medical sciences
Mesocricetus
methylene blue
Methylene Blue - toxicity
Transfection
Tumors
title Morphological transformation by 8-hydroxy-2'-deoxyguanosine in Syrian hamster embryo (SHE) cells
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