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Is There a Significant Role for Lipid Peroxidation in the Causation of Malignancy and for Antioxidants in Cancer Prevention?¹

Free Radical Research Group, Division of Biochemistry, United Medical and Dental School, Guy's Hospital, University of London, London SE1 9RT, United Kingdom [A.T.D., C.A.R-E.], and Department of Bioscience and Biotechnology, University of Strathclyde, Glasgow G4 ONR, United Kingdom [R.H.B.]

-Tocopherol (-T) uptake and its relationship to cell proliferation and lipid peroxidation was studied in a baby hamster kidney cell line (BHK-21/C13) and its polyoma virus-transformed malignant counterpart (BHK-21/PyY cells). The principal findings were as follows. (a) The level of lipid peroxidation judged by malondialdehyde (MDA) measurement by HPLC, was higher in the transformed cells than in the nontransformed cells. Oxidative stress by 374 mM Fe³⁺/10 mM ADP caused a significant increase in the level of MDA of a similar magnitude in both cell types. Addition of 7, 14, and 21 mM -T caused no diminution of the MDA level in the unstressed cells and abolished the increase in MDA seen in the stressed cells. (b) The endogenous level of -T in the transformed cells was lower than in the nontransformed cells and all of the measurable -T in these cells was destroyed by the oxidative stress. Supplementation of the cells with -T caused an increase in the level of -T that was proportional to the level of inclusion of -T in the medium. (c) Growth was stimulated by 7 and 14 mM -T but not by the higher levels of inclusion in the medium. The growth stimulation was much larger in the transformed cells (163% of growth in the unsupplemented medium) than in the nontransformed cells (120%). (d) These results demonstrate that, in this cell system, the growth-stimulating ability of -T is unrelated to the ability of -T to control lipid peroxidation and that the level of peroxidation is increased in the malignant state. The difference between the findings reported here and earlier work showing increased levels of -T and decreased levels of peroxidation in transformed malignant cells is discussed and possible explanations for it are advanced.