Acrylonitrile-induced morphological transformation in Syrian hamster embryo cells.
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 microg/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 microg/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.
Zhang
H
H
Division of Toxicology, Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Kamendulis
L M
LM
Jiang
J
J
Xu
Y
Y
Klaunig
J E
JE
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000181:Acrylonitrile / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D006224:Cricetinae; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects; D005260:Female; D008647:Mesocricetus; D017382:Reactive Oxygen Species; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D017382:Reactive Oxygen Species; D014810:Vitamin E; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine; D000181:Acrylonitrile