Acrylonitrile-induced morphological transformation in Syrian hamster embryo cells

Acrylonitrile (ACN) is a monomer used in the synthesis of rubber, fibers an d 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 complet ely elucidated, investigations by our group and others have suggested a rol e for the induction of oxidative stress and the resultant oxidative damage in this process, In vitro cell transformation models are useful for detecti ng and studying the mechanisms of chemical carcinogenesis. Cell transformat ion by chemical carcinogens in Syrian hamster embryo (SHE) cells exhibits a multistage process similar to that observed in vivo, for both non-genotoxi c and genotoxic carcinogens. In the present study, the ability of ACN to in duce 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 mu g/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 inhi bited by co-treatment with the antioxidants alpha-tocopherol and (-)-epigal locathechin-3 gallate (EGCG) for 7 days. Treatment of SHE cells with 75 mu g/ml ACN produced a significant increase in 8-hydroxy-2'-deoxyguanosine tha t was also inhibited by co-treatment with alpha-tocopherol or EGCG, These r esults support the proposal that oxidative stress and the resulting oxidati ve damage is involved in ACN-induced carcinogenicity.