The Effects of Antioxidants on the Induction of Malignant Transformation in Vitro
There is now much evidence to suggest that free radicals play a role in malignant transformation. Several of the agents which suppress malignant transformation in vivo and in vitro may do so by inhibiting free radical reactions, either by prevention of free radical induction/formation (presumably, the action of protease inhibitors) or by the detoxification of free radicals through a variety of mechanisms. The agents we’ve studied which have effects on radiation induced transformation in vitro and are known to have a role in free radical detoxifying reactions include: catalase, superoxide dismutase, selenium, vitamin E, dimethylsulfoxide and several copper containing compounds such as CuDIPS (Cu II) (3,5-diisopropyl-salicylate2), cuprous chloride and cupric chloride.
There is currently much interest in the role of free radicals in tumor promotion in vivo and in vitro. Several of the known biological effects of the potent tumor promoter, 12-0-tetradecanoyl-phorbol-13-acetate (TPA), are known to be antagonized by agents which interact with free radicals, such as antioxidants. We have observed that in vitro promotion by TPA can be enhanced by the presence of ferrous ions (Fe2+) in the cellular medium. It is known that TPA treatment of cells results in the production of \(0_2 \bar \cdot\) and H202. As ferrous ions (Fe2+) are necessary for the conversion of H202 to OH·, via a Fenton-type reaction, it is possible that at least some of the cellular effects attributable to TPA could be brought about by the interaction of hydroxyl radicals with cellular components. If OH· is the primary damaging free radical species leading to promotion, it is not surprising that agents such as antioxidants suppress promotion.
KeywordsToxicity Hydrogen Peroxide Hydroxyl Hydrocarbon Superoxide
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