EFFECT OF FREE FATTY-ACIDS ON 2-STAGE SKIN CARCINOGENESIS IN MICE

The effect of n-3 and n-6 free fatty acids on two stage skin carcinoge nesis in mice was studied. Stearic, linoleic, arachidonic, and eicosap entaenoic acids inhibited both initiation and promotion stages of skin carcinogenesis. Although no direct correlation between lipid peroxida tion and papilloma formation was observed, a trend towards an increase in the formation of lipid peroxides with the inhibitory effect of fat ty acids on papilloma development was noted. In general, the fatty aci ds applied were incorporated mainly into the phospholipid and free fat ty acid pools. All the fatty acids tested, except eicosapentaenoic and docosahexaenoic acids, inhibited the binding of benzo[a]pyrene (BP) t o DNA. On the other hand, BP and croton oil-induced skin cell prolifer ation was not influenced by any of the fatty acids used. In conclusion , the results of the present study suggest that inhibition of papillom a formation by free fatty acids is complex and can be attributed to a limited extent only to their ability to inhibit BP binding to DNA, to block cell proliferation and enhance the lipid peroxidation process.