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Carcinogenesis, Vol. 21, No. 4, 727-733, April 2000
© 2000 Oxford University Press


Carcinogenesis

Acrylonitrile-induced morphological transformation in Syrian hamster embryo cells

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

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

Acrylonitrile (ACN) is a monomer used in the synthesis of rubber, fibers and plastics. Previous studies demonstrated that ACN induces brain neoplasms (predominately astrocytomas) in rats following chronic treatment. While the mechanisms of ACN-induced glial cell carcinogenicity have not been completely elucidated, investigations by our group and others have suggested a role for the induction of oxidative stress and the resultant oxidative damage in this process. In vitro cell transformation models are useful for detecting and studying the mechanisms of chemical carcinogenesis. Cell transformation by chemical carcinogens in Syrian hamster embryo (SHE) cells exhibits a multistage process similar to that observed in vivo, for both non-genotoxic and genotoxic carcinogens. In the present study, the ability of ACN to induce morphological transformation and oxidative damage was examined in SHE cells. ACN induced an increase in morphological transformation at doses of 50, 62.5 and 75 µg/ml (maximum sub-toxic dose tested) following 7 days of continuous treatment. SHE cells exposed to ACN for 24 h failed to increase morphological transformation. Morphological transformation by ACN was inhibited by co-treatment with the antioxidants {alpha}-tocopherol and (–)-epigallocathechin-3 gallate (EGCG) for 7 days. Treatment of SHE cells with 75 µg/ml ACN produced a significant increase in 8-hydroxy-2'-deoxyguanosine that was also inhibited by co-treatment with {alpha}-tocopherol or EGCG. These results support the proposal that oxidative stress and the resulting oxidative damage is involved in ACN-induced carcinogenicity.


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Toxicol SciHome page
H. Zhang, L. M. Kamendulis, and J. E. Klaunig
Mechanisms for the Induction of Oxidative Stress in Syrian Hamster Embryo Cells by Acrylonitrile
Toxicol. Sci., June 1, 2002; 67(2): 247 - 255.
[Abstract] [Full Text] [PDF]


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CarcinogenesisHome page
H. Xue, R. M. Aziz, N. Sun, J. M. Cassady, L. M. Kamendulis, Y. Xu, G. D. Stoner, and J. E. Klaunig
Inhibition of cellular transformation by berry extracts
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[Abstract] [Full Text] [PDF]



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