IS THERE A SIGNIFICANT ROLE FOR LIPID-PEROXIDATION IN THE CAUSATION OF MALIGNANCY AND FOR ANTIOXIDANTS IN CANCER PREVENTION

Alpha-tocopherol (alpha-T) uptake and its relationship to cell prolife ration and lipid peroxidation was studied in a baby hamster kidney cel l line (BHK-21/C13) and its polyoma virus-transformed malignant counte rpart (BHK-21/PyY cells). The principal findings were as follows. (a) The level of lipid peroxidation judged by malondialdehyde (MDA) measur ement by HPLC, was higher in the transformed cells than in the nontran sformed cells. Oxidative stress by 374 mM Fe3+/10 mM ADP caused a sign ificant increase in the level of MDA of a similar magnitude in both ce ll types. Addition of 7, 14, and 21 mm alpha-T caused no diminution of the MDA level in the unstressed cells and abolished the increase in M DA seen in the stressed cells. (b) The endogenous level of alpha-T in the transformed cells was lower than in the nontransformed cells and a ll of the measurable alpha-T in these cells was destroyed by the oxida tive stress. Supplementation of the cells with alpha-T caused an incre ase in the level of alpha-T that was proportional to the level of incl usion of alpha-T in the medium. (c) Growth was stimulated by 7 and 14 mm alpha-T but not by the higher levels of inclusion in the medium. Th e 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 alpha-T is unrelated to the ability of a lpha-T to control lipid peroxidation and that the level of peroxidatio n is increased in the malignant state. The difference between the find ings reported here and earlier work showing increased levels of alpha- T and decreased levels of peroxidation in transformed malignant cells is discussed and possible explanations for it are advanced.