AIM A large body of evidence has shown that transformation of Syrian hamster embryo(SHE) cell cultures is perhaps the most biologically relevant short term system for identifying carcinogens and studying the mechanisms of chemical carcinogenesis. The purpose of the present study is to examine the ability of aristolochic acid(AA), the active component of many herbal medicines derived from Aristolochia to induce morphological transformation(MT) in cultured SHE cells. In addition, the effect of α tocopherol on AA induced MT was studied. METHODS Prior to the transformation assay, a dose range finding study was conducted employing a wide range of concentrations of AA following either a 24 h or a 7 d treatment to establish an appropriate range of concentrations for the cell transformation assay. AA concentrations causing approximately 0%-50% cytotoxicity were chosen for testing in the cell transformation assay. The effect of α tocopherol on AA induced MT was investigated by co treatment of the cultured SHE cells with transforming concentrations of AA and 100 μmol·L -1 α tocopherol. RESULTS Following a 7 d continuous treatment, AA induced significant increases in MT at concentrations of 0.4, 0.8 and 1.6 mg·L -1 (maximum sub toxic concentration tested). Significant increases in MT were also observed in SHE cells treated with AA at concentrations of 1.0, 1.5, 2.5, 4.5 and 5.0 mg·L -1 (maximum subtoxic concentration tested) for 24 h.
Transformation induced by AA was inhibited (16%-76%) by co treatment with the antioxidant, α tocopherol (100 μmol·L -1 ). CONCLUSION The results of the present study show that AA can induce MT in cultured SHE cells following either a 24 h treatment or a 7 d continuous treatment. MT induced by AA can be inhibited by antioxidant, α tocopherol, suggesting that oxidative stress be involved in AA induced transformation and carcinogenesis. The present study also shows that the SHE cell Received date: 2003 11 03 Accepted date: 2004 01 08 Biography: ZHANG Hai Zhou(1967-), male, native of Dongying, Shandong Province, PhD, MPH, main research field is genetic toxicology and mechanisms of chemical carcinogenesis. *Corresponding author. E mail: haizhou.zhang@covance.com Tel: 1 703 245 2200 Fax: 1 703 759 5782 transformation assay can be a useful tool for the nutraceutical and herbal medicine industry to detect potential carcinogenic ingredients as well as to screen potential anticarcinogenic ingredients in their products.