Diets rich in
omega-3 fatty acids (FA) have been associated with lowered risks of developing certain types of
cancers. We earlier reported that in transgenic mice prone to develop
breast cancer (BCa), a diet supplemented with
canola oil, rich in omega-3-rich FA (as opposed to an omega-6-rich diet containing
corn oil), reduced the risk of developing BCa, and also significantly reduced the incidence of BCa in F1 offspring. To investigate the underlying mechanisms of the
cancer protective effect of
canola oil in the F1 generation, we designed and performed the present study with the same diets using BALB/c mice to remove any possible effect of the transgene. First, we observed epigenetic changes at the genome-wide scale in F1 offspring of mothers fed diets containing omega-3 FAs, including a significant increase in acetylation of H3K18 histone mark and a decrease in H3K4me2 mark on
nucleosomes around transcription start sites. These epigenetic modifications contribute to differential gene expressions associated with various pathways and molecular mechanisms involved in preventing
cancer development, including p53 pathway, G2M checkpoint, DNA repair, inflammatory response, and apoptosis. When offspring mice were exposed to
7,12-Dimethylbenz(a)anthracene (DMBA), the group of mice exposed to a
canola oil (with omega 3 FAs)-rich maternal diet showed delayed mortality, increased survival, reduced lateral
tumor growth, and smaller
tumor size. Remarkably, various genes, including BRCA genes, appear to be epigenetically re-programmed to poise genes to be ready for a rapid transcriptional activation due to the
canola oil-rich maternal diet. This ability to respond rapidly due to epigenetic potentiation appeared to contribute to and promote protection against
breast cancer after
carcinogen exposure.