Selected fatty acids as possible intermediates for selective cytotoxic activity of anticancer agents involving oxygen radicals.

Both polyunsaturated fatty acids (PUFAs) and certain anticancer agents can generate peroxides leading to extensive lipid peroxidation. The link between peroxides, PUFAs and cell killing has been examined by testing the susceptibility of tumor cells to peroxides generated by PUFAs. Our results demonstrate that gammalinolenic, arachidonic and eicosapentaenoic acids are highly effective in killing human breast, lung, and prostate tumor cells while leaving normal cells viable. The availability of PUFAs and the role of lipoperoxidation are discussed with respect to the cytotoxic action of anticancer agents involving oxygen radicals. The results suggest that tumor cell susceptibility to lipid peroxides can be selectively modulated and manipulated by dietary PUFAs, especially those with 3 or more double bonds, and that the suggestion that non-selective toxicities of drugs are mediated by lipid peroxides must be viewed with caution.