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Toxicological Sciences 68, 437-443 (2002)
Copyright © 2002 by the Society of Toxicology

MOLECULAR AND GENETIC TOXICOLOGY

Morphological Transformation and Oxidative Stress Induced by Cyanide in Syrian Hamster Embryo (SHE) Cells

Lisa M. Kamendulis, Haizhou Zhang, Yanhong Wang and James E. Klaunig,1

Division of Toxicology, Department of Pharmacology and Toxicology, Indiana University School of Medicine, 635 Barnhill Dr., MS 1021, Indianapolis, Indiana 46202

Cyanide is a well-established poison known for its rapid lethal action and toxicity. Although long-term mammalian studies examining the carcinogenic potential of cyanide have not been previously reported, cyanide was reported to be positive in Salmonella typhimurium mutagenesis assay and induced aneuploidy in Drosophila. To further evaluate the carcinogenic potential of cyanide, the ability of cyanide to induce morphological transformation in Syrian hamster embryo (SHE) cells was studied. Cyanide induced a dose-dependent increase in morphological transformation in SHE cells following a 7-day continuous treatment. A significant increase in transformation was observed at potassium cyanide doses of 200 µM and greater. Transformation induced by cyanide was inhibited in a dose-related manner by vitamin E, suggesting a role of oxidative stress in the induction of morphological transformation by cyanide. Further, it was shown that 500 µM cyanide induced oxidative DNA damage in SHE cells, evidenced by the formation of 8-hydroxy-2‘-deoxyguanosine (50–66% increase over control). The induction of oxidative stress by cyanide involved an early and temporal inhibition of antioxidant enzymes (catalase and superoxide dismutase) as well as an increased production of reactive oxygen species (1.5- to 2.0-fold over control).

Key Words: catalase; cyanide; morphological transformation; oxidative stress; SHE cells; superoxide dismutase.


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