Mutagenicity of ω-3 fatty acid peroxidation products in the Ames test

Polyunsaturated fatty acids (PUFA) represent one of the main building blocks of cellular membranes and their varying composition impacts lifespan as well as susceptibility to cancer and other degenerative diseases. Increased intake of ω-3 PUFA is taught to compensate for the abundance of ω-6 PUFA in modern human diet and prevent cardiocirculatory diseases. However, highly unsaturated PUFA of marine and seed origin easily oxidize to aldehydic products which form DNA adducts. With increased PUFA consumption it is prudent to re-evaluate ω-3 PUFA safety and the genotoxic hazards of their metabolites. We have used the standard Ames test to examine the mutagenicity of 2 hexenals derived from lipid peroxidation of the common ω-3 PUFA in human diet and tissues. Both 4-hydroxyhexenal and 2-hexenal derived from the ω-3 docosahexaenoic and α-linolenic acid, respectively, induced base substitutions in the TA104 and TA100 Ames strains in a dose dependent manner. Their mutagenicity was dependent on the Y-family DNA polymerase RI and they did not induce other types of mutations such as the -2 and -1 frameshifts in the TA98 and TA97 strains. Our results expand previous findings about the mutagenicity of related ω-3 peroxidation product 4-oxohexenal and raise alert that overuse of ω-3 rich oils may have adverse effect on genome stability.